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Sample records for premix insulin analogues

  1. Glycemic control with insulin glargine plus insulin glulisine versus premixed insulin analogues in real-world practices: a cost-effectiveness study with a randomized pragmatic trial design.

    PubMed

    Levin, Philip A; Zhang, Quanwu; Mersey, James H; Lee, Francis Y; Bromberger, Lee A; Bhushan, Madhu; Bhushan, Rajat

    2011-07-01

    Cost can be an important consideration, along with safety and efficacy, in deciding the most appropriate treatment for patients with type 2 diabetes. Both basal-bolus and premixed insulin analogue regimens are widely used in clinical practice; however, limited information is available regarding cost-effectiveness. The goal of this study was to compare glycemic control, cost-effectiveness, and quality of life effects of insulin glargine plus insulin glulisine (glargine/glulisine) versus premixed insulin analogues in real-world clinical practice. Adults with type 2 diabetes (glycosylated hemoglobin [HbA(1c)] ≥7.0%) at 3 US endocrinology centers were randomly assigned to receive either glargine/glulisine or premixed insulin analogues and continued treatment following the centers' usual practice. HbA(1c), weight, insulin dose, concomitant oral antidiabetic drug (OAD) usage, and hypoglycemia were evaluated at baseline and 3, 6, and 9 months. Medication costs, including costs for all insulin or OAD regimens, were estimated using published wholesale acquisition costs. A total of 197 patients were randomized to receive glargine/glulisine therapy (n = 106) or premixed analogue therapy (n = 91). Overall, the mean age was 56 years, the mean duration of diabetes was 13 years, with a mean HbA(1c) of 9.25% and mean BMI of 35.8 kg/m(2) at baseline. Patients randomized to receive glargine/glulisine had a greater mean HbA(1c) reduction from baseline (-2.3%) than patients receiving a premixed analogue regimen (-1.7%). Adjusted mean follow-up HbA(1c) was 6.9% versus 7.5%, respectively (difference, -0.59%; P < 0.01). The glargine/glulisine group also used a lower mean number of OADs (0.86 vs 1.14; difference, -0.28; P = 0.04) but had a higher weight (240 vs 235 lb; difference, 4.55 lb; P = 0.03) than the premixed analogue group at follow-up. There were no significant differences in daily insulin dose and rates of hypoglycemia. Overall medication costs per 1.0% reduction in HbA(1c

  2. Generalised insulin oedema after intensification of treatment with insulin analogues.

    PubMed

    Adamo, Luigi; Thoelke, Mark

    2013-02-20

    We report a case of generalised insulin oedema after intensification of treatment with genetically modified insulin. This is the first case of generalised oedema in response to treatment with insulin analogues in a patient not insulin naive.

  3. TREATMENT OF TYPE 2 DIABETES WITH BIPHASIC INSULIN ANALOGUES

    PubMed Central

    Rizvi, Ali A.

    2016-01-01

    The majority of patients with Type 2 diabetes require insulin therapy for treating hyperglycaemia. There are several regimens available for insulin initiation and maintenance. Insulin analogues have been developed to mimic normal physiology as closely as possible. Biphasic analogues can target both fasting and postprandial hyperglycaemia, with the added advantage of being premixed and thus convenient for the patient. A practical and feasible option is to initiate insulin with one or more biphasic preparations at mealtimes, thus providing both basal and prandial coverage. Individual titration of dose and frequency of daily injections with biphasic insulin preparations has the potential for improving glycaemic control with a high degree of patient acceptance. Drawbacks include a more rigid regimen, a relative lack of flexibility, and a somewhat higher degree of glycaemic variability and hypoglycaemia when compared to multiple daily basal-bolus injections. Awareness of the advantages and limitations of biphasic insulin analogues can assist clinicians in their appropriate use for the treatment of patients with Type 2 diabetes. PMID:27918600

  4. Insulin analogues: action profiles beyond glycaemic control.

    PubMed

    Eckardt, Kristin; Eckel, Jürgen

    2008-02-01

    A variety of studies have documented significant improvements in the treatment of type 1 and 2 diabetes after the introduction of artificial insulins. This review gives an overview of insulin analogues which are currently approved for therapeutical use. Clinical data regarding the efficiency to control blood glucose level as well as improving HbA1c level in comparison to conventional insulin preparations in type 1 and 2 diabetic patients are summarized. Furthermore, special features of insulin analogues regarding their signalling properties are discussed with focus on the proliferative effects of insulin glargine as well as some recent data of insulin detemir.

  5. Comparison of Basal-Bolus and Premixed Insulin Regimens in Hospitalized Patients With Type 2 Diabetes

    PubMed Central

    Suarez, Lorena; Rodriguez, Maria Galiana; Sanchez, Cecilia; Dieguez, Marta; Riestra, Maria; Casal, Florentino; Delgado, Elias; Menendez, Edelmiro; Umpierrez, Guillermo E.

    2015-01-01

    OBJECTIVE Premixed insulin is a commonly prescribed formulation for the outpatient management of patients with type 2 diabetes. The safety and efficacy of premixed insulin formulations in the hospital setting is not known. RESEARCH DESIGN AND METHODS In a prospective, open-label trial, we randomized general medicine and surgery patients to receive a basal-bolus regimen with glargine once daily and glulisine before meals (n = 33) or premixed human insulin (30% regular insulin and 70% NPH insulin) twice daily (n = 39). Major outcomes included differences in daily blood glucose (BG) levels and frequency of hypoglycemic events (<70 mg/dL) between treatment groups. RESULTS At the first prespecified interim analysis, the study was stopped early because of an increased frequency of hypoglycemia >50% in patients treated with premixed human insulin. A total of 64% of patients treated with premixed insulin experienced one or more episodes of hypoglycemia compared with 24% in the basal-bolus group (P < 0.001). There were no differences in mean daily BG level after the first day of insulin treatment (175 ± 32 vs. 179 ± 43 mg/dL, P = 0.64) between groups. A BG target between 80 and 180 mg/dL before meals was achieved in 55.9% of BG readings in the basal-bolus group and 54.3% of BG readings in the premixed insulin group (P = 0.23). There was no difference in the length of hospital stay or mortality between treatment groups. CONCLUSIONS Inpatient treatment with premixed human insulin resulted in similar glycemic control but in significantly higher frequency of hypoglycemia compared with treatment with basal-bolus insulin regimen in hospitalized patients with diabetes. PMID:26459273

  6. Engineering of Insulin Receptor Isoform-Selective Insulin Analogues

    PubMed Central

    Glendorf, Tine; Stidsen, Carsten E.; Norrman, Mathias; Nishimura, Erica; Sørensen, Anders R.; Kjeldsen, Thomas

    2011-01-01

    Background The insulin receptor (IR) exists in two isoforms, A and B, and the isoform expression pattern is tissue-specific. The C-terminus of the insulin B chain is important for receptor binding and has been shown to contact the IR just adjacent to the region where the A and B isoforms differ. The aim of this study was to investigate the importance of the C-terminus of the B chain in IR isoform binding in order to explore the possibility of engineering tissue-specific/liver-specific insulin analogues. Methodology/Principal Findings Insulin analogue libraries were constructed by total amino acid scanning mutagenesis. The relative binding affinities for the A and B isoform of the IR were determined by competition assays using scintillation proximity assay technology. Structural information was obtained by X-ray crystallography. Introduction of B25A or B25N mutations resulted in analogues with a 2-fold preference for the B compared to the A isoform, whereas the opposite was observed with a B25Y substitution. An acidic amino acid residue at position B27 caused an additional 2-fold selective increase in affinity for the receptor B isoform for analogues bearing a B25N mutation. Furthermore, the combination of B25H with either B27D or B27E also resulted in B isoform-preferential analogues (2-fold preference) even though the corresponding single mutation analogues displayed no differences in relative isoform binding affinity. Conclusions/Significance We have discovered a new class of IR isoform-selective insulin analogues with 2–4-fold differences in relative binding affinities for either the A or the B isoform of the IR compared to human insulin. Our results demonstrate that a mutation at position B25 alone or in combination with a mutation at position B27 in the insulin molecule confers IR isoform selectivity. Isoform-preferential analogues may provide new opportunities for developing insulin analogues with improved clinical benefits. PMID:21625452

  7. Management of Type 2 diabetes in Ramadan: Low-ratio premix insulin working group practical advice

    PubMed Central

    Hassanein, Mohamed; Belhadj, Mohamed; Abdallah, Khalifa; Bhattacharya, Arpan D.; Singh, Awadhesh K.; Tayeb, Khaled; Al-Arouj, Monira; Elghweiry, Awad; Iraqi, Hinde; Nazeer, Mohamed; Jamoussi, Henda; Mnif, Mouna; Al-Madani, Abdulrazzaq; Al-Ali, Hossam; Ligthelm, Robert

    2014-01-01

    The challenge of insulin use during Ramadan could be minimized, if people with diabetes are metabolically stable and are provided with structured education for at least 2–3 months pre-Ramadan. Although, American diabetes association (ADA) recommendations 2010 and South Asian Consensus Guideline 2012 deal with management of diabetes in Ramadan and changes in insulin dosage, no specific guidance on widely prescribed low-ratio premix insulin is currently available. Hence, the working group for insulin therapy in Ramadan, after collective analysis, evaluation, and opinion from clinical practice, have formulated a practical advice to empower physicians with pre-Ramadan preparation, dose adjustment, and treatment algorithm for self-titration of low-ratio premix insulin. PMID:25364673

  8. Cost-effectiveness of insulin analogues for diabetes mellitus.

    PubMed

    Cameron, Chris G; Bennett, Heather A

    2009-02-17

    Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins. However, they are costly alternatives. We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults. We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model. We compared rapid-acting analogues (insulin aspart and insulin lispro) with regular human insulin, and long-acting analogues (insulin glargine and insulin detemir) with neutral protamine Hagedorn insulin. We derived clinical information for the comparisons from meta-analyses of randomized controlled trials. We obtained cost and utility estimates from published sources. We performed sensitivity analyses to test the robustness of our results. For type 1 diabetes, insulin aspart was more effective and less costly than regular human insulin. Insulin lispro was associated with an incremental cost of Can$28,996 per quality-adjusted life-year. The incremental cost per quality-adjusted life-year was Can$87,932 for insulin glargine and Can$387,729 for insulin detemir, compared with neutral protamine Hagedorn insulin. For type 2 diabetes, insulin aspart was associated with an incremental cost of Can$22,488 per quality-adjusted life-year compared with regular human insulin. For insulin lispro, the incremental cost was Can$130,865. Compared with neutral protamine Hagedorn insulin, insulin detemir was less effective and more costly. Insulin glargine was associated with an incremental cost of Can$642,994 per quality-adjusted life-year. The model was sensitive to changes in the effect size of hemoglobin A(1c) and to decrements applied to utility scores when fear of hypoglycemia was included as a factor. The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2

  9. Current european regulatory perspectives on insulin analogues

    PubMed Central

    2011-01-01

    Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions. PMID:21736748

  10. Insulin Analogs or Premixed Insulin Analogs in Combination With Oral Agents for Treatment of Type 2 Diabetes

    PubMed Central

    Levy, Philip

    2007-01-01

    Context Type 2 diabetes is a progressive disease that is reaching epidemic proportions. Whereas most patients are initially managed with oral antidiabetic agents (OADs), the majority eventually require insulin to maintain glycemic control. The availability of insulin analogs (rapid-acting, long-acting, and premixed), with more predictable time-action profiles than human insulin preparations and simple-to-use insulin delivery devices, can help ease the transition to insulin therapy, which is often delayed until glycemic control has been inadequate for several years. >Objective To review the rationale for and strategies to initiate therapy with insulin analogs earlier in the course of type 2 diabetes. Practical barriers that must be overcome to successfully initiate insulin therapy in patients with type 2 diabetes are also briefly described. Design Narrative review of clinical evidence and current diabetes treatment guidelines. Setting and Patients Outpatients with type 2 diabetes inadequately managed with OADs alone. Interventions Three of the most common approaches to initiating insulin therapy with analogs are considered, with clinical evidence and detailed dosing algorithms provided. These approaches include: (1) addition of a basal insulin analog to oral therapy to reduce and stabilize fasting plasma glucose, (2) supplementation of oral therapy with a rapid-acting mealtime insulin analog to control postprandial glucose excursions, and (3) addition of or switching to a premixed insulin analog, which can be used to control both fasting and postprandial glucose in 1 injection. Conclusions Selection of appropriate insulin analog regimens and individualization of therapy can help patients achieve recommended glycemic goals while minimizing hypoglycemia. Education about the eventual need for insulin and improvements in insulin preparations and delivery systems at the time of diagnosis can also help overcome patient barriers. PMID:17955068

  11. Glycaemic control with modified intensive insulin injections (MII) using insulin pens and premixed insulin in children with type-1 diabetes: a randomized controlled trial.

    PubMed

    Soliman, Ashraf T; Omar, Magdi; Rizk, Mostafa M; El Awwa, Ahmad; AlGhobashy, Fatma M

    2006-08-01

    The objective of this study was to compare glycemic control and insulin dosage in children with type 1 diabetes treated by a modified intensified insulin therapy MII using insulin pens (and premixed and regular insulin) with those on conventional insulin therapy. This was a longitudinal, randomized controlled trial for 6 months or more. From a cohort of 125 children with previously diagnosed type-1 diabetes (more than a year after diagnosis) two groups were randomly selected Group AI (n=20) and Group B (n=20). Group AI children and 10 children with recently diagnosed type 1 diabetes (Group AII) were allocated to MII using regular insulin and premixed insulin (30/70 and 40/60 and 50/50). Group B patients continued their conventional insulin therapy for the whole period of the trial. The main outcome measures were glycemic control measured by mean blood glucose concentration and percentage of glycated haemoglobin and total daily insulin dose. Mean blood glucose concentrations before the three main meals, and at midnight, (148, 147, 179 and 127 mg/dl, respectively) were lower in children receiving intensified MII compared with those receiving conventional insulin therapy (192, 174, 194 and 179 mg/dl, respectively) (standardized mean difference 34+/-15 mg/dl), equivalent to a difference of 1.9+/-0.8 mmol/l. This improved control during MII was achieved with no change in the average daily insulin dose in group-AI. In group-AII insulin dose decreased significantly during their first 6 moths of treatment (honeymooning). Glycemic control is better during MII using insulin pens and premixed and regular insulin compared with conventional insulin therapy, without any significant change in insulin dose needed to achieve this level of control. The difference in glycemic control between the two methods is significant and could reduce the risk of micro-vascular complications.

  12. PROGENS-HbA1c study: safety and effectiveness of premixed recombinant human insulin (Gensulin M30)

    PubMed Central

    Walicka, Magdalena; Jóźwiak, Jacek; Rzeszotarski, Jacek; Zarzycka-Lindner, Grażyna; Zonenberg, Anna; Bijoś, Paweł; Masierek, Małgorzata

    2016-01-01

    Introduction Insulin analogues have gained widespread popularity. However, in many countries the use of these drugs is limited by their relatively high cost, so there is still a need for more cost-effective human insulin therapies. The aim of the study was to assess the effectiveness and safety of the premixed recombinant human insulin (rhuI) Gensulin M30 in a real-life setting. Material and methods The study group consisted of 4257 patients (2196 female, 2061 male) with type 2 diabetes, aged 63.7 ±9.4, with body mass index (BMI) 30.3 ±4.5 kg/m2 and diabetes duration 9 ±5.5 years. All patients were treated with premixed rhuI Gensulin M30. In 91.7% of patients, insulin was used in combination with metformin. In 3.7% of patients, it was used with sulphonylureas. The patients were observed for a period of 6 months. Results The total insulin dose on visit 1 was 36.1 ±18.7 U (0.42 ±0.22 U/kg), and by the end of the study it reached 40.3 ±18.9 U (0.48 ±0.22 U/kg). A significant, continuous decrease of the levels of glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose, was observed during the study period. The frequency of hypoglycemia increased slightly during the study, although these figures remained low, especially with regard to severe hypoglycemic episodes (0.02 episodes/patient/year). The lowest number of hypoglycemic episodes occurred in patients treated with insulin and metformin, while the highest number of episodes was observed in patients treated with insulin alone. No weight changes were noted in the patients during the study. Conclusions This study shows rhuI Gensulin M30 to be effective and safe in a real-life setting. PMID:27695488

  13. Review of Insulin and its Analogues in Diabetes Mellitus

    PubMed Central

    Mane, Krishnappa; Chaluvaraju, KC; Niranjan, MS; Zaranappa, TR; Manjuthej, TR

    2012-01-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin’s, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  14. Recombinant DNA derived monomeric insulin analogue: comparison with soluble human insulin in normal subjects.

    PubMed Central

    Vora, J. P.; Owens, D. R.; Dolben, J.; Atiea, J. A.; Dean, J. D.; Kang, S.; Burch, A.; Brange, J.

    1988-01-01

    OBJECTIVE--To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology. DESIGN--Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue. SETTING--Study in normal people at a diabetes research unit and a university department of medical physics. SUBJECTS--Seven healthy male volunteers aged 20-39 not receiving any other drugs. INTERVENTIONS--After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days. END POINT--To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U

  15. Are insulin analogues an unavoidable necessity for the treatment of type 2 diabetes in developing countries? The case of Jordan.

    PubMed

    Hyassat, D; Al Shekarchi, N; Jaddou, H; Liswi, M; El-Khateeb, M; Ajlouni, K M

    2015-12-13

    Despite their reported benefits in terms of glycaemic control, insulin analogues are expensive for patients in developing countries. This study in Jordan aimed to compare the effectiveness and adverse events of premixed human insulin (BHI30) versus premixed insulin analogue (BIAsp30) in patients with type 2 diabetes. In a retrospective cohort study from October 2012 to March 2013, outcomes (HbA1c, weight, hypoglycaemia and lipohypertrophy) were compared at baseline and 6 months after treatment in 628 patients. BHI30 produced a significantly greater reduction in HbA1c than did BIAsp30. This difference in HbA1c remained significant after controlling for the effects of age, sex, duration of diabetes, body mass index and hypoglycaemia (β-coefficient was -0.18 in favour of BHI30). Weight gain and mild hypoglycaemia was significantly higher with BHI30 than with BIAsp30. BHI30 achieved better reduction in HbA1c compared with BIAsp30, with less cost, slightly more weight gain and greater reported mild hypoglycaemia.

  16. Recombinant canine single chain insulin analogues: insulin receptor binding capacity and ability to stimulate glucose uptake.

    PubMed

    Adams, Jamie P; Holder, Angela L; Catchpole, Brian

    2014-12-01

    Virtually all diabetic dogs require exogenous insulin therapy to control their hyperglycaemia. In the UK, the only licensed insulin product currently available is a purified porcine insulin preparation. Recombinant insulin is somewhat problematic in terms of its manufacture, since the gene product (preproinsulin) undergoes substantial post-translational modification in pancreatic β cells before it becomes biologically active. The aim of the present study was to develop recombinant canine single chain insulin (SCI) analogues that could be produced in a prokaryotic expression system and which would require minimal processing. Three recombinant SCI constructs were developed in a prokaryotic expression vector, by replacing the insulin C-peptide sequence with one encoding a synthetic peptide (GGGPGKR), or with one of two insulin-like growth factor (IGF)-2 C-peptide coding sequences (human: SRVSRRSR; canine: SRVTRRSSR). Recombinant proteins were expressed in the periplasmic fraction of Escherichia coli and assessed for their ability to bind to the insulin and IGF-1 receptors, and to stimulate glucose uptake in 3T3-L1 adipocytes. All three recombinant SCI analogues demonstrated preferential binding to the insulin receptor compared to the IGF-1 receptor, with increased binding compared to recombinant canine proinsulin. The recombinant SCI analogues stimulated glucose uptake in 3T3-L1 adipocytes compared to negligible uptake using recombinant canine proinsulin, with the canine insulin/cIGF-2 chimaeric SCI analogue demonstrating the greatest effect. Thus, biologically-active recombinant canine SCI analogues can be produced relatively easily in bacteria, which could potentially be used for treatment of diabetic dogs.

  17. Cysteine analogues potentiate glucose-induced insulin release in vitro

    SciTech Connect

    Ammon, H.P.; Hehl, K.H.; Enz, G.; Setiadi-Ranti, A.; Verspohl, E.J.

    1986-12-01

    In rat pancreatic islets, cysteine analogues, including glutathione, acetylcysteine, cysteamine, D-penicillamine, L-cysteine ethyl ester, and cysteine-potentiated glucose (11.1 mM) induced insulin secretion in a concentration-dependent manner. Their maximal effects were similar and occurred at approximately 0.05, 0.05, 0.1, 0.5, 1.0, 1.0 mM, respectively. At substimulatory glucose levels (2.8 mM), insulin release was not affected by these compounds. In contrast, thiol compounds, structurally different from cysteine and its analogues, such as mesna, tiopronin, meso-2,3-dimercaptosuccinic acid (DMSA), dimercaprol (BAL), beta-thio-D-glucose, as well as those cysteine analogues that lack a free-thiol group, including L-cystine, cystamine, D-penicillamine disulfide, S-carbocysteine, and S-carbamoyl-L-cysteine, did not enhance insulin release at stimulatory glucose levels (11.1 mM); cystine (5 mM) was inhibitory. These in vitro data indicate that among the thiols tested here, only cysteine and its analogues potentiate glucose-induced insulin secretion, whereas thiols that are structurally not related to cysteine do not. This suggests that a cysteine moiety in the molecule is necessary for the insulinotropic effect. For their synergistic action to glucose, the availability of a sulfhydryl group is also a prerequisite. The maximal synergistic action is similar for all cysteine analogues tested, whereas the potency of action is different, suggesting similarity in the mechanism of action but differences in the affinity to the secretory system.

  18. Glycemic control and safety in Chinese patients with type 2 diabetes mellitus who switched from premixed insulin to insulin glargine plus oral antidiabetics: a large, prospective, observational study.

    PubMed

    Zhang, Bo; Zhao, Jing; Yang, Wenying

    2017-03-01

    In some circumstances, the premixed insulin should be switched to alternative therapy. The effectiveness and the safety of switching from premixed insulin to insulin glargine plus oral antidiabetic drugs (OADs) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been clarified and, hence, will be assessed in this study. Chinese patients with T2DM (2013 men and women aged 18-75 years) who had received premixed insulin ± OADs for ≥3 months with glycated hemoglobin (HbA1c) ≤ 10% were enrolled in a prospective, observational study conducted at 53 hospitals across China. At baseline and at the discretion of the physician, patients switched from premixed insulin to insulin glargine plus OADs. Changes in HbA1c, fasting plasma glucose (FPG), 2-hour postprandial glucose (PPG), treatment satisfaction, and the incidence of hypoglycemia were assessed for 16 weeks. In total, 1850 patients completed the study. Mean HbA1c level for the group decreased significantly (from 7.8% ± 1.2% at week 1 to 7.0% ± 1.0% at week 16; P < .0001), and 55.2% of patients achieved HbA1c < 7% at week 16. Mean FPG and 2-hour PPG decreased significantly (-1.4 ± 2.2 and -2.1 ± 3.9 mmol/L, respectively; both P < .0001), whereas patient satisfaction improved significantly. Adverse events were reported in 18.7% of patients. Chinese patients with T2DM who switched from premixed insulin to insulin glargine plus OADs achieved significantly improved glycemic control and treatment satisfaction with a low incidence of hypoglycemia. Patients who are most likely to achieve the HbA1c target less than 7% are younger, have shorter disease duration, and have lower baseline HbA1c and FPG levels.

  19. Cost effectiveness of insulin glargine plus oral antidiabetes drugs compared with premixed insulin alone in patients with type 2 diabetes mellitus in Canada.

    PubMed

    Tunis, Sandra L; Sauriol, Luc; Minshall, Michael E

    2010-01-01

    Several treatment options are available for patients with type 2 diabetes mellitus who are making the transition from oral antidiabetes drugs (OADs) to insulin. Two options currently recommended by the Canadian Diabetes Association for initiating insulin therapy in patients with type 2 diabetes who are no longer responsive to OADs alone are insulin glargine plus OADs, and premixed insulin therapy only. Because of differences in efficacy, adverse events (such as hypoglycaemia) and acquisition costs, these two treatment options may lead to different long-term clinical and economic outcomes. To determine the cost effectiveness of insulin glargine plus OADs compared with premixed insulin without OADs in insulin-naive patients with type 2 diabetes in Canada. Using treatment effects taken from a published clinical trial, the validated IMS-CORE Diabetes Model was used to simulate the long-term cost effectiveness of insulin glargine with OADs, versus premixed insulin. Input treatment effects for the two therapeutic approaches were based on changes in glycosylated haemoglobin A(1c) (HbA(1c)) at clinical trial endpoint, and hypoglycaemia rates. The analysis was conducted from the perspective of the Canadian Provincial payer. Direct treatment and complication costs were obtained from published sources (primarily from Ontario) and reported in $Can, year 2008 values. All base-case costs and outcomes were discounted at 5% per year. Sensitivity analyses were conducted around key parameters and assumptions used in the study. Outcomes included direct medical costs associated with both treatment and diabetes-related complications. Cost-effectiveness outcomes included total average lifetime (35 years) costs, life expectancy (LE), QALYs and incremental cost-effectiveness ratios (ICERs). Base-case analyses showed that, compared with premixed insulin only, insulin glargine in combination with OADs was associated with a 0.051-year increase in LE and a 0.043 increase in QALYs. Insulin

  20. Insulin aspart in a 30/70 premixed formulation. Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture.

    PubMed

    Weyer, C; Heise, T; Heinemann, L

    1997-10-01

    To study the pharmacodynamic properties of a 30/70 premixed formulation of the rapid-acting insulin analog insulin aspart (B28Asp) and its protamine-retarded preparation (30/70 IA) in comparison with a respective mixture of soluble human insulin and NPH insulin (30/70 HI). In this single-center double-blind euglycemic glucose-clamp study, 24 healthy male volunteers (age, 26 +/- 2 years; BMI, 23.7 +/- 1.7 kg/m2) received single subcutaneous injections of 0.3 U/kg body wt of either 30/70 IA or 30/70 HI on 2 study days in randomized order. Glucose infusion rates (GIRs) were determined over a 24-h period after administration. The injection of 30/70 IA resulted in an earlier onset and more pronounced peak of action (tmax, 127 +/- 24 min; GIRmax 9.7 +/- 2.3 mg.kg-1.min-1) than 30/70 HI (tmax, 185 +/- 52 min; GIRmax, 7.4 +/- 1.7 mg.kg-1.min-1_ (P < 0.001). The metabolic activity of 30/70 IA (measured as the sum of the glucose infused) within the first 4 h after injection was 37% greater than that of 30/70 HI (P < 0.0001), while the total metabolic potencies over 24 h of both preparations were comparable. The 30/70 premixed formulation of insulin aspart shows a significantly greater metabolic effect in the first 4 h after subcutaneous injection than the 30/70 mixture of human insulin. Insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation.

  1. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    PubMed

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  2. Interactions of short-acting, intermediate-acting and pre-mixed human insulins with free radicals--Comparative EPR examination.

    PubMed

    Olczyk, Paweł; Komosinska-Vassev, Katarzyna; Ramos, Paweł; Mencner, Łukasz; Olczyk, Krystyna; Pilawa, Barbara

    2015-07-25

    Electron paramagnetic resonance (EPR) spectroscopy was used to examine insulins interactions with free radicals. Human recombinant DNA insulins of three groups were studied: short-acting insulin (Insuman Rapid); intermediate-acting insulins (Humulin N, Insuman Basal), and pre-mixed insulins (Humulin M3, Gensulin M50, Gensulin M40, Gensulin M30). The aim of an X-band (9.3GHz) study was comparative analysis of antioxidative properties of the three groups of human insulins. DPPH was used as a stable free radical model. Amplitudes of EPR lines of DPPH as the paramagnetic free radical reference, and DPPH interacting with the individual tested insulins were compared. For all the examined insulins kinetics of their interactions with free radicals up to 60 min were obtained. The strongest interactions with free radicals were observed for the short-acting insulin - Insuman Rapid. The lowest interactions with free radicals were characteristic for intermediate-acting insulin - Insuman Basal. The pre-mixed insulins i.e. Humulin M3 and Gensulin M50 revealed the fastest interactions with free radicals. The short acting, intermediate acting and premixed insulins have been found to be effective agents in reducing free radical formation in vitro and should be further considered as potential useful tools in attenuation of oxidative stress in diabetic patients. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Therapeutics of Diabetes Mellitus: Focus on Insulin Analogues and Insulin Pumps

    PubMed Central

    Valla, Vasiliki

    2010-01-01

    Aim. Inadequately controlled diabetes accounts for chronic complications and increases mortality. Its therapeutic management aims in normal HbA1C, prandial and postprandial glucose levels. This review discusses diabetes management focusing on the latest insulin analogues, alternative insulin delivery systems and the artificial pancreas. Results. Intensive insulin therapy with multiple daily injections (MDI) allows better imitation of the physiological rhythm of insulin secretion. Longer-acting, basal insulin analogues provide concomitant improvements in safety, efficacy and variability of glycaemic control, followed by low risks of hypoglycaemia. Continuous subcutaneous insulin infusion (CSII) provides long-term glycaemic control especially in type 1 diabetic patients, while reducing hypoglycaemic episodes and glycaemic variability. Continuous subcutaneous glucose monitoring (CGM) systems provide information on postprandial glucose excursions and nocturnal hypo- and/or hyperglycemias. This information enhances treatment options, provides a useful tool for self-monitoring and allows safer achievement of treatment targets. In the absence of a cure-like pancreas or islets transplants, artificial “closed-loop” systems mimicking the pancreatic activity have been also developed. Conclusions. Individualized treatment plans for insulin initiation and administration mode are critical in achieving target glycaemic levels. Progress in these fields is expected to facilitate and improve the quality of life of diabetic patients. PMID:20589066

  4. Use of insulin immunoassays in clinical studies involving rapid-acting insulin analogues: Bi-insulin IRMA preliminary assessment.

    PubMed

    Agin, Arnaud; Jeandidier, Nathalie; Gasser, Françoise; Grucker, Daniel; Sapin, Rémy

    2006-01-01

    In clinical studies involving rapid-acting analogues (RAAs), insulin immunoreactivity is frequently measured, including endogenous, regular insulin (RI) and RAA immunoreactivities. Such a procedure implies equivalent cross-reactivities of all insulins present in serum. Commercially available human insulin immunoassays have been widely used, but their limitations (including hemolysis and anti-insulin antibodies) were not fully investigated. The aims of our study were to compare cross-reactivities of RI and RAAs in buffer and in serum and to investigate insulin immunoassay pitfalls. Cross-reactivities were assessed using Bi-insulin IRMA (Schering Cis-Bio International) in phosphate-buffered saline (PBS)-1% bovine serum albumin (BSA) and in pools of sera spiked with RI and RAAs (lispro and aspart). To investigate the influence of hemolysis, a pool of sera spiked with RAA was mixed with a concentrated hemolysate (final hemoglobin concentration 10 g/L) and incubated for 3 h at room temperature. To determine interference by anti-insulin antibodies, insulin was removed using charcoal from 18 sera with anti-insulin antibodies and from 17 sera without detectable anti-insulin antibodies. These insulin-free samples were then spiked with RI and RAAs and the immunoreactivity was determined. Compared with buffer, cross-reactivity in serum for RI, lispro and aspart was lower (35%, 29% and 26% lower, respectively). Hemolysis degraded almost all RI and RAAs contained in the serum (>or=95%). Anti-insulin antibody interference was significant for RI and RAAs (pinsulin antibody level in the serum (pinsulin antibodies should be removed from samples before immunoreactivity measurements.

  5. Insulin analogues in pregnancy and specific congenital anomalies: a literature review.

    PubMed

    de Jong, Josta; Garne, Ester; Wender-Ozegowska, Ewa; Morgan, Margery; de Jong-van den Berg, Lolkje T W; Wang, Hao

    2016-05-01

    Insulin analogues are commonly used in pregnant women with diabetes. It is not known if the use of insulin analogues in pregnancy is associated with any higher risk of congenital anomalies in the offspring compared with use of human insulin. We performed a literature search for studies of pregnant women with pregestational diabetes using insulin analogues in the first trimester and information on congenital anomalies. The studies were analysed to compare the congenital anomaly rate among foetuses of mothers using insulin analogues with foetuses of mothers using human insulin. Of 29 studies, we included 1286 foetuses of mothers using short-acting insulin analogues with 1089 references of mothers using human insulin and 768 foetuses of mothers using long-acting insulin analogues with 685 references of mothers using long-acting human insulin (Neutral Protamine Hagedorn). The congenital anomaly rate was 4.84% and 4.29% among the foetuses of mothers using lispro and aspart. For glargine and detemir, the congenital anomaly rate was 2.86% and 3.47%, respectively. No studies on the use of insulin glulisine and degludec in pregnancy were found. There was no statistically significant difference in the congenital anomaly rate among foetuses exposed to insulin analogues (lispro, aspart, glargine or detemir) compared with those exposed to human insulin or Neutral Protamine Hagedorn insulin. The total prevalence of congenital anomalies was not increased for foetuses exposed to insulin analogues. The small samples in the included studies provided insufficient statistical power to identify a moderate increased risk of specific congenital anomalies.

  6. Systematic Evaluation of the Metabolic to Mitogenic Potency Ratio for B10-Substituted Insulin Analogues

    PubMed Central

    Glendorf, Tine; Knudsen, Louise; Stidsen, Carsten E.; Hansen, Bo F.; Hegelund, Anne Charlotte; Sørensen, Anders R.; Nishimura, Erica; Kjeldsen, Thomas

    2012-01-01

    Background Insulin analogues comprising acidic amino acid substitutions at position B10 have previously been shown to display increased mitogenic potencies compared to human insulin and the underlying molecular mechanisms have been subject to much scrutiny and debate. However, B10 is still an attractive position for amino acid substitutions given its important role in hexamer formation. The aim of this study was to investigate the relationships between the receptor binding properties as well as the metabolic and mitogenic potencies of a series of insulin analogues with different amino acid substitutions at position B10 and to identify a B10-substituted insulin analogue without an increased mitogenic to metabolic potency ratio. Methodology/Principal Findings A panel of ten singly-substituted B10 insulin analogues with different amino acid side chain characteristics were prepared and insulin receptor (both isoforms) and IGF-I receptor binding affinities using purified receptors, insulin receptor dissociation rates using BHK cells over-expressing the human insulin receptor, metabolic potencies by lipogenesis in isolated rat adipocytes, and mitogenic potencies using two different cell types predominantly expressing either the insulin or the IGF-I receptor were systematically investigated. Only analogues B10D and B10E with significantly increased insulin and IGF-I receptor affinities as well as decreased insulin receptor dissociation rates displayed enhanced mitogenic potencies in both cell types employed. For the remaining analogues with less pronounced changes in receptor affinities and insulin receptor dissociation rates, no apparent correlation between insulin receptor occupancy time and mitogenicity was observed. Conclusions/Significance Several B10-substituted insulin analogues devoid of disproportionate increases in mitogenic compared to metabolic potencies were identified. In the present study, receptor binding affinity rather than insulin receptor off

  7. Continuous subcutaneous insulin infusion with short-acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost-effectiveness.

    PubMed

    Radermecker, Régis Pierre; Scheen, André Jacques

    2004-01-01

    Portable insulin infusion devices are effective and safe insulin delivery systems for managing diabetes mellitus, especially type 1 diabetes. Rapidly absorbed insulin analogues, such as insulin lispro or insulin aspart, may offer an advantage over regular human insulin for insulin pumps. Several open-label randomised crossover trials demonstrated that continuous subcutaneous insulin infusion (CSII) with insulin lispro provided a better control of postprandial hyperglycaemia and a slightly but significantly lower glycated haemoglobin level, with lower daily insulin requirement and similar or even less hypoglycaemic episodes. A CSII study comparing insulin lispro and insulin aspart demonstrated similar results with the two analogues, and better results than those with regular insulin. Because these analogues have a quicker onset and a shorter duration of action than regular insulin, one might expect an earlier and greater metabolic deterioration in case of CSII interruption, but a more rapid correction of metabolic abnormalities after insulin boluses when reactivating the pump. These expectations were confirmed in randomised protocols comparing the metabolic changes occurring during and after CSII interruption of various durations when the pump infused either insulin lispro or regular insulin. The extra cost resulting from the use of CSII and insulin analogues in diabetes management should be compensated for by better metabolic control and quality of life. In conclusion, CSII delivering fast-acting insulin analogues may be considered as one of the best methods to replace insulin in a physiological manner by mimicking meal and basal insulin requirements, without higher risk of hypoglycaemia or ketoacidosis in well-educated diabetic patients.

  8. [Reflections of a clinician on the switch from human to analogue insulin treatment].

    PubMed

    Deák, László

    2012-10-07

    The development of insulin therapy has not been stopped since the manufacturing of human insulin, because better mimic of physiological insulin response made it necessary to modify the human insulin molecule in order to create rapidly absorbing insulin analogues and 24-hour acting basal insulin analogues. Clinical observations indicate that the complete switch from human basal-bolus therapy to insulin analogues means not only "unit-for-unit" switch but it represents a transfer to an insulin therapy with different basal/bolus ratio as a result of different pharmacokinetic and pharmacodynamic properties of insulin and the level of insulin resistance of the patient. With reference to a case-history, the author presents his experience on a switch from human insulin to insulin analogue. Furthermore, the author summarizes data obtained from a few cases reported in international literature which draw the attention to the fact that the basal/bolus ratio should be adjusted individually, which may be the key for the success in the therapy in these cases.

  9. Premixed vs basal-bolus insulin regimen in Type 2 diabetes: comparison of clinical outcomes from randomized controlled trials and real-world data.

    PubMed

    Anyanwagu, U; Mamza, J; Gordon, J; Donnelly, R; Idris, I

    2017-09-25

    To evaluate the concordance between data derived from randomized controlled trial (RCT) and real-world estimates of HbA1c and weight change after 24 weeks of initiation of a basal-bolus compared with a premixed insulin regimen in people with Type 2 diabetes. Data eight RCTs were pooled after a systematic review of studies examining basal-bolus (n = 1893) or premixed (n = 1517) regimens. Real-world data were extracted from the UK primary care dataset for people on basal-bolus (n = 7483) or premixed insulin regimens (n=10 744). The mean differences between HbA1c and weight from baseline were calculated using t-tests, while analysis of variance was used to compare the two populations. Linear regression analyses were used to determine the predictors of this change. Both insulin regimens were associated with HbA1c reductions (real-world data -0.28%; RCT data, -1.4%) and weight gain (real-world data, +0.27 kg; RCT data, +2.96 kg) but there were no significant differences between basal-bolus and premixed insulin. Discordances in the pattern of treatment response were observed, however, between real-world and RCT data for both insulin regimens. For any given baseline HbA1c concentration, the change in HbA1c in the RCTs was greater than in real-world conditions and for those with baseline weight above ~60 kg, RCT data showed overall weight gain in contrast to slight weight loss in the real-world population. Lastly, for both randomized controlled trial and real-world populations, while greater baseline weight was associated with reduced response to treatment, the association was much steeper in the RCT than in the real-world population. In addition, greater baseline weight was associated with greater weight reductions after both premixed insulin and basal-bolus insulin regimens, although to a lesser extent with the latter. These results highlight discrepancies between real-world outcomes and RCT results with respect to starting basal-bolus insulin therapy (which is lower in

  10. Evidence-based clinical use of insulin premixtures

    PubMed Central

    2013-01-01

    Brazil is expected to have 19.6 million patients with diabetes by the year 2030. A key concept in the treatment of type 2 diabetes mellitus (T2DM) is establishing individualized glycemic goals based on each patient’s clinical characteristics, which impact the choice of antihyperglycemic therapy. Targets for glycemic control, including fasting blood glucose, postprandial blood glucose, and glycated hemoglobin (A1C), are often not reached solely with antihyperglycemic therapy, and insulin therapy is often required. Basal insulin is considered an initial strategy; however, premixed insulins are convenient and are equally or more effective, especially for patients who require both basal and prandial control but desire a more simplified strategy involving fewer daily injections than a basal-bolus regimen. Most physicians are reluctant to transition patients to insulin treatment due to inappropriate assumptions and insufficient information. We conducted a nonsystematic review in PubMed and identified the most relevant and recently published articles that compared the use of premixed insulin versus basal insulin analogues used alone or in combination with rapid-acting insulin analogues before meals in patients with T2DM. These studies suggest that premixed insulin analogues are equally or more effective in reducing A1C compared to basal insulin analogues alone in spite of the small increase in the risk of nonsevere hypoglycemic events and nonclinically significant weight gain. Premixed insulin analogues can be used in insulin-naïve patients, in patients already on basal insulin therapy, and those using basal-bolus therapy who are noncompliant with blood glucose self-monitoring and titration of multiple insulin doses. We additionally provide practical aspects related to titration for the specific premixed insulin analogue formulations commercially available in Brazil. PMID:24011173

  11. Insulin analogues may accelerate progression of diabetic retinopathy after impairment of inner blood-retinal barrier.

    PubMed

    Kaya, Abdullah; Kar, Taner; Aksoy, Yakup; Özalper, Veysel; Başbuğ, Barbaros

    2013-12-01

    Diabetic retinopathy regresses after spontaneous infarction or surgical ablation of pituitary gland. Growth hormone deficiency seems to be a protective factor for development of diabetic retinopathy in dwarfs. Despite the same glycemic control, development of diabetic retinopathy is significantly higher in pubertal subjects than pre-pubertal subjects. These evidences indicate a strong relationship between growth hormone and progression of diabetic retinopathy. Insulin like growth factor-1 (IGF-1) is the most important mediator of effects of growth hormone (GH). It stimulates IGF-1 receptor. Insulin analogues also stimulate IGF-1 receptor. Therefore insulin analogues may show similar effects like growth hormone and deteriorate diabetic retinopathy. However we suggest that impairment degree of inner blood-retinal barrier should be considered for this claim. We hypothesize that insulin analogues have dual effects (beneficial and worsening) depending on stage of impairment of inner blood-retinal barrier. Insulin analogues protect pericytes and blood-retinal barrier by decreasing blood glucose level. Analogues may pass into the retinal tissue in very low amounts when inner blood-retinal barrier is intact. Therefore, insulin analogues may not deteriorate diabetic retinopathy but also have beneficial effect by protecting blood-retinal barrier at this stage. However, they may pass into the retinal tissue in much more amounts when inner blood-retinal barrier impairs. Analogues may deteriorate cellular composition of retina through stimulation of IGF-1 receptors. A number of different cell types, including glia, retinal pigment epithelial cells and fibroblast-like cells have been identified in diabetic epiretinal tissues. Insulin analogues may cause proliferation in these cells. A type of glial cell named Non-astrocytic Inner Retinal Glia-like (NIRG) cell was identified to be stimulated and proliferate by IGF-1. IGF has been reported to generate traction force in retinal

  12. Adherence to premixed insulin in a prefilled pen compared with a vial/syringe in people with diabetes in Singapore.

    PubMed

    Cheen, Hua Heng McVin; Lim, Seng Han; Huang, Ming Chien; Bee, Yong Mong; Wee, Hwee Lin

    2014-07-01

    The real-world clinical effectiveness of exogenous insulin is limited by nonadherence. Various insulin delivery systems have been developed to help improve adherence, with prefilled pens gaining popularity among adult Singaporeans with diabetes. However, adherence to insulin in people with diabetes in Singapore and most of Asia has not been studied. This study aimed to compare adherence to premixed insulin formulated in a prefilled pen versus a vial/syringe and to identify predictors of adherence in 955 patients managed at the outpatient clinics of the largest acute care hospital in Singapore. In this retrospective longitudinal study, electronic medical and pharmacy refill records were used to determine adherence to insulin over 24 months, measured in terms of compliance and persistence. Compliance is expressed as the medication possession ratio (used as continuous and categorical variables), and persistence is reported as a dichotomous variable with a permissible refill gap of 30 days before discontinuation of therapy is considered. Multivariate linear or logistic regression analysis was used to identify predictors of adherence. Compared with prefilled pen users, vial/syringe users were older (mean [SD] age, 64.1 [10.6] vs 62.4 [11.9] years; P = 0.032), and more were undergoing polypharmacy (69.6% vs 54.1%; P < 0.001). The mean (SD) medication possession ratio was comparable in vial/syringe versus prefilled pen users (83.8% [26.9%] vs 86.0% [23.2%]; P = 0.266). Prefilled pen users were more persistent with therapy compared with vial/syringe users (odds ratio = 1.36; 95% CI, 1.01-1.86) after adjusting for sociodemographic and clinical covariates. Median time to discontinuation of therapy was comparable (vial/syringe vs prefilled pen: 409 vs 532 days; P = 0.076). Being managed by an endocrinologist and not receiving government subsidies were significant predictors of persistence. Compared with other studies that found strong associations between adherence and

  13. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism

    PubMed Central

    Redwan, Elrashdy M.; Linjawi, Moustafa H.; Uversky, Vladimir N.

    2016-01-01

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein? PMID:26983499

  14. Simultaneous determination of insulin and its analogues in pharmaceutical formulations by micellar electrokinetic chromatography.

    PubMed

    Lamalle, Caroline; Servais, Anne-Catherine; Radermecker, Régis P; Crommen, Jacques; Fillet, Marianne

    2015-01-01

    A simple and efficient MEKC method was developed to simultaneously determine human insulin, its five analogues, the main degradation products and the excipients usually present in injection formulations. A very fast method with a total analysis time of 3 min was then successfully validated for the analysis of human insulin and the quality control of commercial formulations was carried out.

  15. Comparison of medication adherence in diabetes mellitus patients on human versus analogue insulins.

    PubMed

    Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro; Echeverri-Cataño, Luis Felipe

    2017-02-01

    Objetive: This study evaluated the results of treatment adherence scales in two cohorts of patients with diabetes mellitus treated either with human or analogue insulins. A cohort study was conducted in diabetes mellitus patients older than 18 that were being treated with human or analogue insulins. Two instruments were applied to each patient [medication possession ratio, Morisky-Green test] to evaluate treatment adherence. A total of 238 patients, were included. The majority (69.4%) of the subjects had human insulin and 30.6% had insulin analogue prescriptions. Out of the total, 163 (68.5%) cases were classified as adherent to therapy, according to the type of insulin, as follows: 69.9% for conventional and 65.3% for analogues; without differences between the groups (CI95%:0.450-1.458). The adherence to treatment was more probable in patients with elementary-secondary education (OR:2.341; CI95%:1.199-4.568) and less probable for those in the age range of 31-45 years (OR:0.427; CI95%:0.187-0.971). The results of this study show that there are no significant statistical differences in adherence when comparing human with analogue insulin therapy. Strategies to improve treatment adherence are particularly important since they improve the clinical results.

  16. Budget Impact of Long-Acting Insulin Analogues: The Case in Brazil

    PubMed Central

    da Silva, Everton Nunes; Pereira, Maurício G

    2016-01-01

    Background Long-acting insulin analogues for type 1 diabetes (T1D) treatment have been available on the Brazilian market since 2002. However, the population cannot access the analogues through the public health system. Objective To estimate the incremental budget impact of long-acting insulin analogues coverage for T1D patients in the Brazilian public health system compared to NPH insulin. Methods We performed a budget impact analysis of a five-year period. The eligible population was projected using epidemiological data from the International Diabetes Federation estimates for patients between 0–14 and 20–79 years old. The prevalence of T1D was estimated in children, and the same proportion was applied to the 15-19-year-old group due to a gap in epidemiological information. We considered 4,944 new cases per year and a 34.61/100,000 inhabitants mortality rate. Market share for long-acting insulin analogues was assumed as 20% in the first year, reaching 40% in the fifth year. The mean daily dose was taken from clinical trials. We calculated the bargaining power of the Ministry of Health by dividing the price paid for human insulin in the last purchase by the average regulated price. We performed univariate and multivariate sensitivity analyses. Results The incremental budget impact of long-acting insulin analogues was US$ 28.6 million in the first year, and reached US$ 58.7 million in the fifth year. The total incremental budget impact was US$ 217.9 million over the five-year period. The sensitivity analysis showed that the percentage of T1D among diabetic adults and the insulin analogue price were the main factors that affected the budget impact. Conclusions The cost of the first year of long-acting insulin analogue coverage would correspond to 0.03% of total public health expenditure. The main advantage of this study is that it identifies potential bargaining power because it features more realistic profiles of resource usage, once centralized purchasing is

  17. Budget Impact of Long-Acting Insulin Analogues: The Case in Brazil.

    PubMed

    Laranjeira, Fernanda O; Silva, Everton Nunes da; Pereira, Maurício G

    2016-01-01

    Long-acting insulin analogues for type 1 diabetes (T1D) treatment have been available on the Brazilian market since 2002. However, the population cannot access the analogues through the public health system. To estimate the incremental budget impact of long-acting insulin analogues coverage for T1D patients in the Brazilian public health system compared to NPH insulin. We performed a budget impact analysis of a five-year period. The eligible population was projected using epidemiological data from the International Diabetes Federation estimates for patients between 0-14 and 20-79 years old. The prevalence of T1D was estimated in children, and the same proportion was applied to the 15-19-year-old group due to a gap in epidemiological information. We considered 4,944 new cases per year and a 34.61/100,000 inhabitants mortality rate. Market share for long-acting insulin analogues was assumed as 20% in the first year, reaching 40% in the fifth year. The mean daily dose was taken from clinical trials. We calculated the bargaining power of the Ministry of Health by dividing the price paid for human insulin in the last purchase by the average regulated price. We performed univariate and multivariate sensitivity analyses. The incremental budget impact of long-acting insulin analogues was US$ 28.6 million in the first year, and reached US$ 58.7 million in the fifth year. The total incremental budget impact was US$ 217.9 million over the five-year period. The sensitivity analysis showed that the percentage of T1D among diabetic adults and the insulin analogue price were the main factors that affected the budget impact. The cost of the first year of long-acting insulin analogue coverage would correspond to 0.03% of total public health expenditure. The main advantage of this study is that it identifies potential bargaining power because it features more realistic profiles of resource usage, once centralized purchasing is established as an economically sustainable strategy

  18. Switching from premixed insulin to glargine-based insulin regimen improves glycaemic control in patients with type 1 or type 2 diabetes: a retrospective primary care-based analysis

    PubMed Central

    Sharplin, Peter; Gordon, Jason; Peters, John R; Tetlow, Anthony P; Longman, Andrea J; McEwan, Philip

    2009-01-01

    Background Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. Methods Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. Results Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c ≥ 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 ± 1.35 U/Kg to 0.88 ± 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 ± 2.51 U/Kg to 0.98 ± 2.58 U/Kg, p < 0.001). Conclusion In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic

  19. Factors associated with reaching or not reaching target HbA1c after initiation of basal or premixed insulin in patients with type 2 diabetes.

    PubMed

    Scheen, A J; Schmitt, H; Jiang, H H; Ivanyi, T

    2017-02-01

    To evaluate factors associated with reaching or not reaching target glycated haemoglobin (HbA1c) levels by analysing the respective contributions of fasting hyperglycaemia (FHG), also referred to as basal hyperglycaemia, vs postprandial hyperglycaemia (PHG) before and after initiation of a basal or premixed insulin regimen in patients with type 2 diabetes. This post-hoc analysis of insulin-naïve patients in the DURABLE study randomised to receive either insulin glargine or insulin lispro mix 25 evaluated the percentages of patients achieving a target HbA1c of <7.0% (<53mmol/mol) per baseline HbA1c quartiles, and the effect of each insulin regimen on the relative contributions of PHG and FHG to overall hyperglycaemia. Patients had comparable demographic characteristics and similar HbA1c and FHG values at baseline in each HbA1c quartile regardless of whether they reached the target HbA1c. The higher the HbA1c quartile, the greater was the decrease in HbA1c, but also the smaller the percentage of patients achieving the target HbA1c. HbA1c and FHG decreased more in patients reaching the target, resulting in significantly lower values at endpoint in all baseline HbA1c quartiles with either insulin treatment. Patients not achieving the target HbA1c had slightly higher insulin doses, but lower total hypoglycaemia rates. Smaller decreases in FHG were associated with not reaching the target HbA1c, suggesting a need to increase basal or premixed insulin doses to achieve targeted fasting plasma glucose and improve patient response before introducing more intensive prandial insulin regimens. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

    PubMed

    Van Der Gugten, J Grace; Wong, Sophia; Holmes, Daniel T

    2016-01-01

    Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 μU/mL in patient serum samples.

  1. Insulin analogues dosing and costs - comparing real-life daily doses of insulin detemir and insulin glargine in type 2 diabetes patients

    PubMed Central

    2012-01-01

    Background The uncertainties regarding dose similarities between basal long-acting insulin analogues remain. Recent real-world studies indicate dose similarities between insulin detemir and insulin glargine, but further studies are still warranted. The aim of this study was to compare real-life daily doses of insulin detemir and insulin glargine in type 2 diabetes patients when administered once daily. Methods We analysed 536 patient cases from general practice (63%) and endocrinological outpatient clinics (37%). A self-administered questionnaire completed by the treating physician was used to obtain data on patient characteristics (gender, age, weight, height, latest HbA1c-value), daily doses, administration of and number of years treated with insulin detemir and insulin glargine, concomitant insulin use and use of non-insulin anti-diabetic medication. Both bivariate analyses and multivariate regression analyses were applied to examine whether there were differences in the daily doses of insulin detemir and insulin glargine. Results There was no significant difference in the mean daily doses of insulin detemir (0.414 U/kg) and insulin glargine (0.416 U/kg) (p = 0.4341). In multivariate regression analyses, age and BMI had a significant influence on daily insulin dose with the dose increasing 0.003 U/kg (p = 0.0375) and 0.008 U/kg (p = 0.0003) with every 1 increment in age and BMI, respectively. Conclusions Dose similarities between insulin detemir and insulin glargine were seen in type 2 diabetes patients when administered once daily. Thus, the use of insulin detemir and insulin glargine is not associated with different medical costs if the price and treating algorithm are similar. PMID:23009558

  2. Doping control analysis of insulin and its analogues in equine plasma by liquid chromatography-tandem mass spectrometry.

    PubMed

    Ho, Emmie N M; Wan, Terence S M; Wong, April S Y; Lam, Kenneth K H; Stewart, Brian D

    2008-08-08

    Insulin administration can increase muscle glycogen by utilising hyperinsulinaemic clamps prior to sports events or during the recovery phases, and increase muscle size by its chalonic action to inhibit protein breakdown. In order to control insulin abuse in equine sports, a method to detect effectively the use of insulins in horses would be required. Besides the readily available human insulin and its synthetic analogues, structurally similar insulins from other species can also be used as doping agents. This study describes a method for the simultaneous detection of bovine, porcine and human insulins, as well as the synthetic analogues Humalog (Lilly) and Novolog (Novo Nordisk) in equine plasma. Insulins were isolated from equine plasma by immunoaffinity purification, followed by centrifugal filtration, and analysed by nano-liquid chromatography-tandem mass spectrometry (LC/MS/MS). Insulin and analogues were detected and confirmed by comparing their retention times and major product ions. All five insulins (human insulin, Humalog, Novolog, bovine insulin and porcine insulin), which are exogenous in the horse, could be detected and confirmed at 0.05ng/mL. This method was successful in confirming the presence of human insulin in plasma collected from horses up to 4h after having been administered a single low dose of recombinant human insulin (Humulin R, Eli Lilly). To our knowledge, this is the first identification of exogenous insulin from post-administration horse plasma samples.

  3. Alternative signaling network activation through different insulin receptor family members caused by pro-mitogenic antidiabetic insulin analogues in human mammary epithelial cells.

    PubMed

    ter Braak, Bas; Wink, Steven; Koedoot, Esmee; Pont, Chantal; Siezen, Christine; van der Laan, Jan Willem; van de Water, Bob

    2015-07-19

    Insulin analogues are designed to have improved pharmacokinetic parameters compared to regular human insulin. This provides a sustained control of blood glucose levels in diabetic patients. All novel insulin analogues are tested for their mitogenic side effects, however these assays do not take into account the molecular mode of action of different insulin analogues. Insulin analogues can bind the insulin receptor and the insulin-like growth factor 1 receptor with different affinities and consequently will activate different downstream signaling pathways. Here we used a panel of MCF7 human breast cancer cell lines that selectively express either one of the isoforms of the INSR or the IGF1R. We applied a transcriptomics approach to assess the differential transcriptional programs activated in these cells by either insulin, IGF1 or X10 treatment. Based on the differentially expressed genes between insulin versus IGF1 and X10 treatment, we retrieved a mitogenic classifier gene set. Validation by RT-qPCR confirmed the robustness of this gene set. The translational potential of these mitogenic classifier genes was examined in primary human mammary cells and in mammary gland tissue of mice in an in vivo model. The predictive power of the classifier genes was evaluated by testing all commercial insulin analogues in the in vitro model and defined X10 and glargine as the most potent mitogenic insulin analogues. We propose that these mitogenic classifier genes can be used to test the mitogenic potential of novel insulin analogues as well as other alternative molecules with an anticipated affinity for the IGF1R.

  4. Why do people appeal to the courts for access to medication? The case of insulin analogues in Bahia (Brazil).

    PubMed

    Lisboa, Erick Soares; Souza, Luis Eugenio Portela Fernandes de

    2017-06-01

    Insulin analogues have been the object of controversy concerning their therapeutic superiority to human insulin. Perhaps, in part, because of this, insulin analogues are frequently the subject of lawsuits. The judicialization of health has been well studied, but little is known about the reasons that lead people to go to the courts to obtain access to medicines on SUS (the Brazilian National Health System). Therefore, this study aims to analyze the reasons that led people to appeal to the courts to obtain access to insulins analogues in the state of Bahia. This is a case study based on documentary sources. Between 2010 and 2013, 149 lawsuits requiring insulin analogues from the state health authority were filed in the courts. The main reasons for the appeal to the courts, cited in the cases, can be grouped into four categories: the users' lack of finances, an essential need for insulin analogue, the duty and obligation of the state to provide them and bureaucratic difficulties. People turned to the courts, mostly, because doctors who accompany their patients have shifted from the official policy, believing that insulin analogues are better than human insulins. They also recognize that the public health system does not distribute them nor does it give doctors the wherewithal to purchase them with their own resources.

  5. Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes.

    PubMed

    Klein, O; Lynge, J; Endahl, L; Damholt, B; Nosek, L; Heise, T

    2007-05-01

    This study compared the time-action profiles of the novel albumin-bound basal insulin analogue NN344 with those of insulin detemir and insulin glargine in individuals with type 2 diabetes. Twenty-seven insulin-treated men with type 2 diabetes [body mass index 30.8 +/- 2.6 kg/m(2) (mean +/- s.d.), haemoglobin A(1c) 7.6 +/- 1.1%] were enrolled in this randomized, double-blind trial and participated in six euglycaemic glucose clamp experiments [target blood glucose (BG) 5 mmol/l] each. Participants received NN344 in three experiments at a dose of 0.8, 1.6 and 2.8 dosing units (DU) (1 DU corresponds to 6 nmol NN344) per kilogram of body weight. In the other three experiments, the participants received 0.4, 0.8 and 1.4 U/kg of either insulin detemir or insulin glargine. The insulin preparations were characterized with regards to their effects on glucose infusion rates (GIRs) (in particular duration of action and within-subject and between-subject variabilities), BG, C-peptide, free fatty acids (FFA), endogenous glucose production (EGP) and peripheral glucose uptake (PGU) over 24 h post-dose. The mean GIR profiles for all three preparations were similar in shape/flatness and showed increasing effect (area under the curve for GIR: AUC-GIR(total)) with increasing dose [low dose: 647 +/- 580, 882 +/- 634, 571 +/- 647 mg/kg (insulin detemir vs. NN344 vs. insulin glargine]; medium dose: 1203 +/- 816, 1720 +/- 1109, 1393 +/- 1203 mg/kg and high dose: 2171 +/- 1344, 3119 +/- 1549, 2952 +/- 2028 mg/kg; p = 0.48]. The duration of action increased with rising doses of all insulin preparations, without major differences between treatments. BG remained below 7 mmol/l in nearly all the experiments. Within-subject variability was lower for the albumin-bound insulin analogues, insulin detemir and NN344, than for insulin glargine (p < 0.0001). Between-subject variability did not differ between treatments, nor did the effects on BG, C-peptide, FFA, EGP or PGU. In individuals with type 2

  6. Demonstrating strategies for initiation of insulin therapy: matching the right insulin to the right patient.

    PubMed

    Meneghini, L

    2008-08-01

    To increase awareness regarding the different types of insulin available and provide discussion regarding how each type of insulin can address the needs of diverse patients in terms of their unique requirements, preferences, medical history and lifestyle concerns. New classes of antidiabetes medications, the development of insulin analogues and novel insulin delivery systems, provide more options for the management of type 2 diabetes. Given the inevitable progression of beta-cell dysfunction, along with the relatively limited glucose-lowering capacity of other agents, many patients will eventually require insulin for optimal glycaemic management. However, patients and physicians often fail to initiate insulin early enough during the progression of disease to maintain the recommended levels of glycaemic control. The inherent properties of the new insulin analogues, more physiological and user-friendly time-action profiles compared with older human insulin formulations, may partly address the barriers to insulin use. Insulin analogues include rapid acting (for prandial glycaemic control), long acting (for basal insulin coverage) and premixed insulin analogues, which combine both a rapid acting and an extended duration component in a single insulin formulation. Various case-based scenarios on initiating and intensifying therapy with insulin analogues will be presented. Development of an individualised treatment plan for initiation of insulin is a critical step in achieving target glycaemic levels in patients with type 2 diabetes.

  7. Doping control analysis of insulin and its analogues in equine urine by liquid chromatography-tandem mass spectrometry.

    PubMed

    Ho, Emmie N M; Wan, Terence S M; Wong, April S Y; Lam, Kenneth K H; Stewart, Brian D

    2011-02-25

    Insulin and its analogues have been banned in both human and equine sports owing to their potential for misuse. Insulin administration can increase muscle glycogen by utilising hyperinsulinaemic clamps prior to sports events or during the recovery phases, and increase muscle size by its chalonic action to inhibit protein breakdown. In order to control insulin abuse in equine sports, a method to effectively detect the use of insulins in horses is required. Besides the readily available human insulin and its synthetic analogues, structurally similar insulins from other species can also be used as doping agents. The author's laboratory has previously reported a method for the detection of bovine, porcine and human insulins, as well as the synthetic analogues Humalog (Lispro) and Novolog (Aspart) in equine plasma. This study describes a complementary method for the simultaneous detection of five exogenous insulins and their possible metabolites in equine urine. Insulins and their possible metabolites were isolated from equine urine by immunoaffinity purification, and analysed by nano liquid chromatography-tandem mass spectrometry (LC/MS/MS). Insulin and its analogues were detected and confirmed by comparing their retention times and major product ions. All five insulins (human insulin, Humalog, Novolog, bovine insulin and porcine insulin), which are exogenous in horse, could be detected and confirmed at 0.05ng/mL. This method was successfully applied to confirm the presence of human insulin in urine collected from horses up to 4h after having been administered a single low dose of recombinant human insulin (Humulin R, Eli Lilly). To our knowledge, this is the first identification of exogenous insulin in post-administration horse urine samples. Copyright © 2010 Elsevier B.V. All rights reserved.

  8. Polymorphic distribution of proteins in solution by mass spectrometry: The analysis of insulin analogues.

    PubMed

    Fávero-Retto, Maely P; Guerreiro, Luiz Henrique; Pessanha, Cássio M; Palmieri, Leonardo C; Lima, Luís Maurício T R

    2017-01-01

    The characterization of conformational and oligomeric distribution of proteins is of paramount importance for the understanding of the correlation between structure and function. Among the bioanalytical approaches currently available, the electrospray ionization-mass spectrometry (ESI-MS) coupled to ion mobility spectrometry (IMS) is the best suited for high resolution identification with high sensitivity, allowing the in situ separation of oligomeric and conformational species. We tested the performance of the ESI-MS technique along with the IMS separation approach on a broad variety of insulin and insulin analogues with distinct oligomeric distribution pattern. The measurement of commercial insulin allowed the identification of species ranging from monomers to hexamers and their complexes with zinc ions. Dissimilar distribution profile for regular insulin as a function of formulation component and among the insulin analogues were observed by ESI-IMS-MS but not by ESI-MS along, crystallographic assays or size-exclusion chromatography. These data suggest the additional suitability of ESI-IMS-MS in conformational and oligomeric profiling of biomacromolecules and biopharmaceuticals. The easiness of the technique provides further motivation for its application in the characterization of both raw and formulated protein biopharmaceuticals in routine and comparability exercises. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  9. [Intensive insulin therapy in type 2 diabetes mellitus].

    PubMed

    Jermendy, György

    2012-09-23

    In the last couple of years, the intensive conservative insulin treatment (basal-bolus regime) became more and more popular even in patients with type 2 diabetes. Using this insulin treatment, continuous patient education, co-operation between the medical team (diabetologist, dietician and diabetes-nurses) and the patient as well as the availability of modern insulins, pens and glucometers are of great importance. Clearly, the basal-bolus treatment with human insulin has advantages over the conservative (conventional) treatment with twice daily premix insulins. Moreover, the basal-bolus treatment with insulin-analogues proved to be superior in some aspects as compared to human insulins. The intensive insulin treatment (basal-bolus regime with insulin-analogues) approaches the optimal insulin substitution and, with its use the adequate correction of each element of the glucose triad (fasting blood glucose, postprandial blood glucose, HbA1c) should be considered feasible even in patients with type 2 diabetes.

  10. Efficacy and safety of a premixed versus a basal-plus insulin regimen as intensification for type 2 diabetes by timing of the main meal.

    PubMed

    Gross, Jorge L; Rojas, Arturo; Shah, Sanjiv; Tinahones, Francisco J; Cleall, Simon; Rodríguez, Angel

    2016-06-01

    To describe the efficacy and safety of premixed insulin lispro protamine suspension 75%/insulin lispro solution 25% (LM25) twice daily (bid) versus basal insulin glargine plus prandial insulin lispro (IGL), both once daily, according to main meal timing. Data were obtained post hoc from a 24 week, randomized, open-label study comparing LM25 and IGL as insulin intensification in patients with type 2 diabetes inadequately controlled with once daily basal insulin glargine plus metformin and/or pioglitazone (ClinicalTrials.gov identifier: NCT01175824). Patients administered LM25 bid before breakfast and the evening meal, insulin glargine at bedtime and insulin lispro before the day's main meal (meal with the highest 2 hour postprandial glucose level during screening). Patients were grouped by main meal. Changes in glycosylated hemoglobin (HbA1c) and bodyweight were summarized using likelihood-based mixed models; hypoglycemia incidence was compared between treatments using Fisher's exact test. Overall, 476 patients (LM25, n = 236; IGL, n = 240) were randomized. In all main meal groups, with both insulin regimens, mean HbA1c significantly decreased from baseline to 24 weeks (p < 0.0001). Patients whose main meal was in the evening had a greater bodyweight increase with LM25 than with IGL (p = 0.015), and a smaller proportion of these patients experienced total (p = 0.027) and nocturnal (p = 0.006) hypoglycemia with LM25 compared with IGL. Patients whose main meal was lunch experienced more nocturnal hypoglycemia with LM25 than with IGL (p = 0.030). Study limitations include that this was a post hoc analysis and no assessments ensured that: SMBG results determined timing of the main meal, each patient's main meal remained unchanged throughout the study, or patients administered insulin lispro with that meal. Glycemic control improved in patients receiving either LM25 or IGL, irrespective of main meal timing. Both regimens can be used in

  11. Effects of rapid-acting insulin analogues insulin glulisine and insulin aspart on postprandial glycemic excursion with single bout of exercise in patients with type 2 diabetes.

    PubMed

    Tanaka, Nagaaki; Hiura, Yoshikazu

    2015-01-01

    The analogue insulin glulisine (Glu) shows both more rapid onset and shorter duration of action compared with the other rapid-acting insulin analogues. The current study investigates these properties in regard to the occurrence of hypoglycemia related to exercise. A randomized, single-center, open-label, crossover study was conducted in 12 hospitalized type 2 diabetes patients (all male, mean ± SD age of 51.9 ± 11.3 years; BMI: 25.5 ± 3.9 kg/m2; HbA1c: 11.2 ± 2.4 %). Glu or insulin aspart (Asp) was subcutaneously administered just before breakfast. Insulin dosage was determined as the usual dose of pre-prandial rapid-acting insulin for patients treated with insulin therapy or as 0.1 unit/kg for patients treated with oral anti-hyperglycemic agents. Sixty min after the start of eating, the patients began aerobic exercise on a bicycle ergometer for 30 min at 50% of maximum heart rate. Hypoglycemic episodes (plasma glucose level < 70 mg/dL with or without symptoms) were observed more frequently in Asp group (p < 0.05). Post-exercise plasma glucose levels at 90, 120, and 150 min were significantly lower in Asp group (p < 0.05). In patients with BMI < 25 kg/m2 (n = 6), post-exercise blood glucose levels were significantly lower in Asp group (p < 0.05), while in patients with BMI ≥ 25 kg/m2 (n = 6) the difference was not significant. Glu may therefore be a suitable choice of rapid-acting insulin for patients with type 2 diabetes who are at high risk of post-exercise hypoglycemia.

  12. Comparative assessment of the efficacy and safety of acarbose and metformin combined with premixed insulin in patients with type 2 diabetes mellitus.

    PubMed

    Wu, Honghua; Liu, Jie; Lou, Qingqing; Liu, Jing; Shen, Li; Zhang, Mingxia; Lv, Xiaofeng; Gu, Mingjun; Guo, Xiaohui

    2017-09-01

    This study, a subgroup analysis of the data from the Organization Program of DiabEtes INsulIN ManaGement study, aimed to compare the efficacy and safety profiles of acarbose and metformin used in combination with premixed insulin.This analysis included 80 and 192 patients taking only 1 oral antidiabetic drug, classified into acarbose (treated with acarbose + insulin) and metformin groups (treated with metformin + insulin), respectively. The efficacy and safety data were analyzed for within- and between-group differences. The clinical trial registry number was NCT01338376.The percentage of patients who achieved target hemoglobin A1c (HbA1c) <7% in the acarbose and metformin groups were 38.75% and 30.73%, respectively, after a 16-week treatment. The average HbA1c levels in the acarbose and metformin groups were comparable at baseline and decreased significantly in both groups at the end of the study. All 7 blood glucose decreased significantly in both groups at endpoint compared with that at baseline. Insulin consumption was higher in the metformin group in terms of total daily amount and units/kg body weight. Incidences of hypoglycemia were similar in both groups. Body weight changed significantly in both groups from baseline to endpoint, but with no significant difference between the groups. Mean scores of Morisky Medication Adherence Scale improved in both groups at endpoint.Combination of insulin with acarbose or metformin could improve glycemic control in patients with type 2 diabetes mellitus. Acarbose and metformin were found to be comparable in terms of efficacy, weight gain, and incidence of hypoglycemia.

  13. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus.

    PubMed

    Ito, Hiroyuki; Abe, Mariko; Antoku, Shinichi; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Mifune, Mizuo; Togane, Michiko

    2014-01-01

    The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. The glycated hemoglobin (HbA1c) level (8.3% ± 1.8% to 8.2% ± 1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤ 8.0% (-0.9 ± 2.0 versus 0.3 ± 0.6, respectively, P = 0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7 ± 3.6 versus -0.8 ± 3.5, P = 0.04). B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT.

  14. Effects of switching from prandial premixed insulin therapy to basal plus two times bolus insulin therapy on glycemic control and quality of life in patients with type 2 diabetes mellitus

    PubMed Central

    Ito, Hiroyuki; Abe, Mariko; Antoku, Shinichi; Omoto, Takashi; Shinozaki, Masahiro; Nishio, Shinya; Mifune, Mizuo; Togane, Michiko

    2014-01-01

    Background The effects of switching from prandial premixed insulin therapy (PPT) injected three times a day to basal plus two times bolus insulin therapy (B2B) on glycemic control and quality of life were investigated in patients with type 2 diabetes mellitus. Methods The clinical course was prospectively observed during the first 16 weeks after switching to B2B (insulin glargine plus insulin glulisine before breakfast and dinner) in 27 subjects previously treated with PPT using 50/50 premixed insulin. The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was administered at the start and end of the study. Results The glycated hemoglobin (HbA1c) level (8.3%±1.8% to 8.2%±1.1%) and the DTSQ score did not change between the start and end of the study. An improvement in HbA1c level was found in nine (33%) subjects. The change in HbA1c showed a significant negative correlation with baseline HbA1c, and was significantly better in patients with a baseline HbA1c >8.0% than in those with an HbA1c ≤8.0% (−0.9±2.0 versus 0.3±0.6, respectively, P=0.02). The change in DTSQ score representing treatment satisfaction was significantly greater in patients whose HbA1c level was improved than in those in whom it was not (2.7±3.6 versus −0.8±3.5, P=0.04). Conclusion B2B was noninferior to PPT with regard to HbA1c levels in patients with type 2 diabetes mellitus. B2B should be considered particularly for subjects whose glycemic control is poor despite PPT. PMID:24790413

  15. Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

    SciTech Connect

    Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, Christopher J.; Turkenburg, Johan P.; Jiráček, Jiří; Brzozowski, Andrzej M.

    2014-10-01

    [AsnB26]- and [GlyB26]-insulin mutants attain a B26-turn like fold without assistance of chemical modifications. Their structures match the insulin receptor interface and expand the spectrum of insulin conformations. The structural characterization of the insulin–insulin receptor (IR) interaction still lacks the conformation of the crucial B21–B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.

  16. A Randomized Trial of Step-up Treatment with Premixed Insulin Lispro-50/50 vs. Aspart-70/30 in Patients with Type 2 Diabetes Mellitus.

    PubMed

    Domeki, Nozomi; Matsumura, Mihoko; Monden, Tsuyoshi; Nakatani, Yuki; Aso, Yoshimasa

    2014-12-01

    When insulin treatment is started in patients with type 2 diabetes mellitus (T2DM), there are many regimens that control serum glucose levels to a normal range. Basal-bolus insulin therapy is one of the most effective treatments for improving glycemic control to prevent the progression of diabetic microvascular complications. This study was conducted to determine whether step-up insulin treatment with premixed insulin aspart-30/70 (BIAsp 30) or lispro-50/50 (Mix50) in Japanese patients with type 2 diabetes mellitus could achieve better glycemic control. In this open label study, 72 insulin-naïve patients with poorly controlled T2DM (HbA1c ≥8.4%), who had been taking oral antidiabetic drugs for at least 12 months, were randomized to receive BIAsp 30 or Mix50 therapy. Patients started treatment of a pre-dinner injection of each type of insulin (Step 1). At 16 ± 2 weeks, a pre-breakfast injection of each type of insulin was added if HbA1c exceeded 7.4% (step 2). If patients had still not achieved HbA1c <7.4% after an additional 16 ± 2 weeks, a pre-lunch insulin injection was added (step 3). Hypoglycemic episodes were also recorded. The cumulative percentages of subjects who achieved HbA1c <7.4% were 36.1% (13/36) for both Mix50 and BIAsp 30 in step 1, 62.9% (23/36) for BIAsp 30 and 52.8% (19/36) for Mix50 in step 2, and 66.7% (24/36) in BIAsp 30 and 72.2% (26/36) in Mix50 in step 3. The achievement rates of HbA1c <7.4% were not statistically different between the two groups. A total of ten hypoglycemic episodes occurred in this study. However, there were no severe hypoglycemic episodes. All cases recovered by taking glucose and drinking juice. Mix50 step-up treatment has a clinical effect in achieving good glycemic control equal to that of BIAsp 30 treatment.

  17. Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex.

    PubMed

    Záková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, Christopher J; Turkenburg, Johan P; Jiráček, Jiří; Brzozowski, Andrzej M

    2014-10-01

    The structural characterization of the insulin-insulin receptor (IR) interaction still lacks the conformation of the crucial B21-B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms.

  18. Pharmacological efficacy of FGF21 analogue, liraglutide and insulin glargine in treatment of type 2 diabetes.

    PubMed

    Ye, Xianlong; Qi, Jianying; Yu, Dan; Wu, Yunzhou; Zhu, Shenglong; Li, Shujie; Wu, Qiang; Ren, Guiping; Li, Deshan

    2017-04-01

    Fibroblast growth factor 21 (FGF21) is a promising regulator of glucose and lipid metabolism with multiple beneficial effects including hypoglycemic and lipid-lowering. Previous studies have reported that FGF21 is expected to become a new drug for treatment of diabetes. Liraglutide and insulin glargine are the two representative anti-diabetic biological drugs. In the current study, we aim to compare the long-term pharmacological efficacy of mFGF21 (an FGF21 analogue), liraglutide and insulin glargine in type 2 diabetic db/db mice. Db/db mice were initially treated with three kinds of proteins (25nmol/kg/day) by subcutaneous injection once a day for 4weeks, then subsequently be treated with once every two days for next 4weeks. After 8weeks of treatments, the blood glucose levels, body weights, glycosylated hemoglobin levels, fasting insulin levels, serum lipid profiles, hepatic biochemical parameters, oral glucose tolerance tests and hepatic mRNA expression levels of several proteins (GK, G6P, GLUT-1 and GLUT-4) associated with glucose metabolism of the experimental mice were detected. Results demonstrated that three proteins could significantly decrease the fed blood glucose levels of db/db mice. After treatment for 1week, the fed blood glucose levels of db/db mice in liraglutide group were significantly lower than those in mFGF21 and insulin glargine groups. However, after 2weeks of administration, the long-lasting hypoglycemic effect of mFGF21 was superior to liraglutide and insulin glargine up to the end of the experiments. Compared with liraglutide and insulin glargine, mFGF21 significantly reduced the glycosylated hemoglobin levels and improved the ability on glycemic control, insulin resistance, serum lipid and liver function states in db/db mice after 8weeks treatments. In addition, mFGF21 regulated glucose metabolism through increasing the mRNA expression levels of GK and GLUT-1, and decreasing the mRNA expression level of G6P. But liraglutide and insulin

  19. Antidiabetic activity of 3-hydroxyflavone analogues in high fructose fed insulin resistant rats

    PubMed Central

    Nayak, Yogendra; Venkatachalam, H.; Daroji, Vijay Kumar; Mathew, Geetha; Jayashree, B.S.; Unnikrishnan, M.K.

    2014-01-01

    Synthetic 3-hydroxyflavone analogues (JY-1, JY-2, JY-3, JY-4), were tested for antidiabetic activity in high-fructose-diet-fed (66 %, for 6 weeks) insulin-resistant Wistar rats (FD-fed rats). The fasting blood glucose, insulin, creatinine and AGEs were decreased to near normal upon treatment with test compounds. Insulin resistance markers such as HOMA-IR, K-ITT, plasma triglycerides, lipids, endogenous antioxidant defense and glycogen were restored in FD-fed rats after treatment with 3-hydroxyflavones. It is known that insulin resistance is partly because of oxidative stress and hence antioxidant activity was determined. They exhibited significant in vitro DPPH and ABTS radical scavenging activity (IC50: 10.66-66.63 µM). Test compounds inhibited ROS and NO production in RAW 264.7 cells (IC50: 10.39–42.63 µM) and they were found as potent as quercetin. Further, the test compounds inhibited lipid peroxidation at low concentrations (IC50: 99.61-217.47 µM). All test compounds at concentrations 100-200 µM protected calf thymus DNA-damage by Fenton reaction. In addition, test compounds inhibited protein glycation in different in vitro antiglycation assays. JY-2 showed maximum potency in all the stages of glycation which was comparable to the standard quercetin and aminoguanidine. Test compounds also enhanced the glucose uptake by L6 myotubes at an EC50 much lower than that of quercetin. Thus the synthetic 3-hydroxyflavones were found to have good antidiabetic activity by pleotropic and multimodal suppression of insulin resistance and enhancement of glucose uptake by skeletal muscles. These compounds are non-toxic at the doses tested. Further, the combined antioxidant and antiglycation activities of these molecules have complementary benefits in management of diabetes. PMID:26417321

  20. Evaluation of the quality of life of patients with diabetes mellitus treated with conventional or analogue insulins.

    PubMed

    Machado-Alba, Jorge Enrique; Medina-Morales, Diego Alejandro; Echeverri-Cataño, Luis Felipe

    2016-06-01

    The results of two scales that measure quality of life of patients with diabetes mellitus treated with conventional or analogue insulin were evaluated and compared. Descriptive, observational, cross-sectional study, conducted in the cities of Pereira and Manizales, Colombia, in a care facility between 1 August 2013 and 30 March 2014. A total of 238 patients diagnosed with diabetes mellitus type 1 or type 2 who had been undergoing treatment with conventional or analogue insulin for at least 6months. Comparison of the results of the Diabetes 39 (specific) and European Quality of Life-5 Dimensions (EQ-5D) (generic) tools it was performed. Comparisons between the results of the two instruments were performed. Tests for parametric and non-parametric distribution (Pearson's correlation coefficient, Mann-Whitney U test, Student's t-test and Wilcoxon test) were used. The mean age was 57.7±16.6years. Conventional insulin was prescribed to 69.6% of patients, and analogue insulin was prescribed to 30.4% of patients. Diabetes-39 (D-39) showed 24.7% of subjects with a high quality of life. No statistically significant differences were found when comparing patients prescribed conventional or analogue insulin (p=0.35; 95% confidence interval [CI]: 0.375-1.419). In the EQ-5D survey, 45.7% claimed to have a high quality of life, without statistically significant differences between groups (p=0.56; 95%CI: 0.676-2.047). No differences between patients receiving conventional insulin versus analogue insulin were detected in terms of quality of life. The group aged over 60years requires special attention to improve their quality of life, and programs should focus on those individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes

    SciTech Connect

    Serri, O.; Beauregard, H.; Brazeau, P.; Abribat, T.; Lambert, J.; Harris, A.; Vachon, L. Sandoz Canada Inc., Dorval, Quebec )

    1991-02-20

    To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, the authors studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 {mu}g/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group than in the placebo group. Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group than in the placebo group. Glycemic control did not change significantly in either group. They conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

  2. Human insulin analogues modified at the B26 site reveal a hormone conformation that is undetected in the receptor complex

    PubMed Central

    Žáková, Lenka; Kletvíková, Emília; Lepšík, Martin; Collinsová, Michaela; Watson, Christopher J.; Turkenburg, Johan P.; Jiráček, Jiří; Brzozowski, Andrzej M.

    2014-01-01

    The structural characterization of the insulin–insulin receptor (IR) interaction still lacks the conformation of the crucial B21–B30 insulin region, which must be different from that in its storage forms to ensure effective receptor binding. Here, it is shown that insulin analogues modified by natural amino acids at the TyrB26 site can represent an active form of this hormone. In particular, [AsnB26]-insulin and [GlyB26]-insulin attain a B26-turn-like conformation that differs from that in all known structures of the native hormone. It also matches the receptor interface, avoiding substantial steric clashes. This indicates that insulin may attain a B26-turn-like conformation upon IR binding. Moreover, there is an unexpected, but significant, binding specificity of the AsnB26 mutant for predominantly the metabolic B isoform of the receptor. As it is correlated with the B26 bend of the B-chain of the hormone, the structures of AsnB26 analogues may provide the first structural insight into the structural origins of differential insulin signalling through insulin receptor A and B isoforms. PMID:25286859

  3. Advances in the quantitation of therapeutic insulin analogues by LC-MS/MS.

    PubMed

    Blackburn, Michael

    2013-12-01

    Insulin analogues represent a major and growing class of biotherapeutics, and their quantitation is an important focus of commercial and public effort across a number of different fields. As LC-MS has developed, it has become an increasingly practicable and desirable alternative to ligand-binding-based approaches for quantitation of this class of compounds. The sensitivity challenge of measuring trace levels of this large peptide molecule in a protein-containing matrix is considerable; however, different approaches to detection, extraction and separation are described to overcome this challenge, including immunoaffinity capture, SPE and low-flow HPLC. Considerations such as bioanalytical assay acceptance criteria and antidrug antibody effects during drug development are included, alongside descriptions of recent sports doping and clinical applications. Factors affecting the correlation and agreement of MS with biological ligand-binding methods are discussed, with ways to anticipate and appreciate differences between the values derived from each technique. The 'future perspective' section discusses the likely trend towards MS-based analysis for these compounds and the impact of HRMS. A high degree of scientific creativity, combined with science-defined regulatory approaches that define suitable validation criteria, will be needed to meet the demanding requirements for high-throughput analysis of insulin by LC-MS.

  4. Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

    PubMed

    Pitocco, D; Rizzi, A; Scavone, G; Tanese, L; Zaccardi, F; Manto, A; Ghirlanda, G

    2013-09-01

    In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

  5. Analysis of alternatives for insulinizing patients to achieve glycemic control and avoid accompanying risks of hypoglycemia.

    PubMed

    Gao, Jialin; Xiong, Qianyin; Miao, Jun; Zhang, Yao; Xia, Libing; Lu, Meiqin; Zhang, Binhua; Chen, Yueping; Zhang, Ansu; Yu, Cui; Wang, Li-Zhuo

    2015-05-01

    The aims of the present study were to explore the efficacy of glycemic control and the risks of hypoglycemia with different methods of insulin therapy, and to provide reference data for the clinical treatment of diabetes. In this retrospective study, hospitalized patients diagnosed with type 2 diabetes between March and December 2014, in the Department of Endocrinology in the First Affiliated Hospital of Wannan Medical College, were divided into three groups, including an intensive insulin analogue therapy group, a premixed insulin analogue treatment group and a premixed human insulin therapy group. The efficacy of glycemic control and the incidence of hypoglycemia were determined in each of the insulin treatment groups. Compared with the other treatment groups, the intensive insulin analogue therapy group was associated with superior blood glucose control, shorter time to reach standard insulin regimen, shorter hospitalization time, fewer fluctuations in blood glucose levels and lower insulin dosage on discharge from hospital. However, this treatment was also associated with a high risk of hypoglycemia. In conclusion, when combined with the effective prevention of hypoglycemia and appropriate nursing care (especially in hospital care), intensive insulin analogue therapy may provide the greatest benefit to patients.

  6. A(1c) control in a primary care setting: self-titrating an insulin analog pre-mix (INITIATEplus trial).

    PubMed

    Oyer, David S; Shepherd, Mark D; Coulter, Franklin C; Bhargava, Anuj; Brett, Jason; Chu, Pei-Ling; Trippe, Bruce S

    2009-11-01

    To study glycemic control and hypoglycemia development upon initiation of insulin through a self-titration schedule in a 24-week trial, conducted with 4875 insulin-naïve patients with poorly controlled type 2 diabetes, predominantly in a primary care setting. Subjects initiated twice-daily biphasic insulin aspart 70/30 with 6 units prebreakfast and 6 units presupper, self-titrating according to self-measured blood glucose values. Subjects were randomized (1:1:1) to telephone counseling provided by a registered dietician: no counseling (NC), 1 counseling session (1C), or 3 sessions (3C). Mean baseline HbA(1c) (9.9% across groups) decreased approximately 2.5% to 7.49% + or - 1.48, 7.48% + or - 1.50, and 7.44% + or - 1.46 in the NC, 1C, and 3C groups, respectively. Within these groups, a hemoglobin A(1c) (HbA(1c)) value <7% was achieved by 40.2%, 41.6%, and 41.8% of subjects, respectively. Eight-point blood glucose profiles were substantially improved from baseline for all groups. Hypoglycemia was experienced by 10.2%-11.4% of the subjects in each group. Rates of minor and major hypoglycemia were low but decreased as dietary counseling increased (minor hypoglycemia: 56 vs 50 vs 45 episodes per 100 patient-years; major hypoglycemia, 9 vs 6 vs 4 episodes per 100 patient-years, for the NC vs 1C vs 3C groups, respectively; P <.001, 3C vs NC). Weight increased by 3.13, 3.40, and 2.88 kg for the NC, 1C, and 3C groups, respectively. In the primary care setting, self-titration of biphasic insulin aspart 70/30 was effective in achieving recommended HbA(1c) goals even with minimal dietary counseling.

  7. Doping control analysis of intact rapid-acting insulin analogues in human urine by liquid chromatography-tandem mass spectrometry.

    PubMed

    Thevis, Mario; Thomas, Andreas; Delahaut, Philippe; Bosseloir, Alain; Schänzer, Wilhelm

    2006-03-15

    Insulin and related synthetic therapeutics have been prohibited by the World Anti-Doping Agency for athletes demonstrably not suffering from diabetes mellitus. The primary specimen for doping controls has been urine, but the renal excretion of intact human insulin as well as synthetic analogues such as the rapid-acting products Humalog LisPro, Novolog Aspart, and Apidra Glulisine has been reported negligible owing to metabolic degradation. Nevertheless, employing solid-phase extraction in combination with immunoaffinity purification followed by a top-down sequencing-based mass spectrometric approach, an assay was established allowing the identification of three intact rapid-acting synthetic insulins in doping control urine samples. A volume of 25 mL of urine was concentrated, insulin analogues were isolated from the concentrate by immunoaffinity chromatography, and the eluate was analyzed using microbore liquid chromatography/tandem mass spectrometry. Characteristic product ion spectra obtained from 5-fold protonated intact analytes as well as isolated insulin B-chains allowed the unambiguous identification of target analytes with detection limits of 0.05 ng/mL (9 fmol/mL). Moreover, assay validation demonstrated recoveries between 72 and 80% for Humalog LisPro, Novolog Aspart, and Apidra Glulisine, and assay precisions ranged from 9 to 16%. A reliable tool is provided that allows the qualitative determination of rapid-acting insulins in urine specimens collected for sports drug testing.

  8. Expression of recombinant human bifunctional peptidylglycine α-amidating monooxygenase in CHO cells and its use for insulin analogue modification.

    PubMed

    Zieliński, Marcin; Wójtowicz-Krawiec, Anna; Mikiewicz, Diana; Kęsik-Brodacka, Małgorzata; Cecuda-Adamczewska, Violetta; Marciniak-Rusek, Alina; Sokołowska, Iwona; Łukasiewicz, Natalia; Gurba, Lidia; Odrowąż-Sypniewski, Michał; Baran, Piotr; Płucienniczak, Grażyna; Płucienniczak, Andrzej; Borowicz, Piotr; Szewczyk, Bogusław

    2016-03-01

    The availability of catalytically active peptidylglycine α-amidating monooxygenase (PAM) should provide the means to examine its potential use for the chemienzymatic synthesis of bioactive peptides for the purpose of pharmacological studies. Hypoglycemic activity is one of the most important features of insulin derivatives. Insulin glargine amide was found to show a time/effect profile which is distinctly more flat and thus more advantageous than insulin glargine itself. The aim of the study was to obtain recombinant PAM and use it for insulin analogue amidation. We stably expressed a recombinant PAM in CHO dhfr-cells in culture. Recombinant PAM was partially purified by fractional ammonium sulphate precipitation and ion-exchange chromatography. The enzyme was used to modify glycine-extended A22(G)-B31(K)-B32(R) human insulin analogue (GKR). Alpha-amidated insulin was analyzed by HPLC and mass spectrometry. Hypoglycemic activity of amidated and non-amidated insulin was compared. The pharmacodynamic effect was based on glucose concentration measurement in Wistar rats with hyperglycemia induced by streptozotocin. The overall glycemic profile up to 36 h was evaluated after subcutaneous single dosing at a range of 2.5-7.5 U/kg b.w. The experiment on rats confirmed with a statistical significance (P < 0.05) hypoglycemic activity of GKR-NH2 in comparison to a control group receiving 0.9% NaCl. Characteristics for GKR-NH2 profile was a rather fast beginning of action (0.5-2.0 h) and quite prolonged return to initial values. GKR-NH2 is a candidate for a hypoglycemic drug product in diabetes care. In addition, this work also provides a valuable alternative method for preparing any other recombinant bioactive peptides with C-terminal amidation.

  9. Improved sensitivity for insulin in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry by premixing alpha-cyano-4-hydroxycinnamic acid matrix with transferrin.

    PubMed

    Kobayashi, Tetsu; Kawai, Hiroshi; Suzuki, Takuo; Kawanishi, Toru; Hayakawa, Takao

    2004-01-01

    This report describes an enhancement of the signal intensities of proteins and peptides in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). When alpha-cyano-4-hydroxycinnamic acid (CHCA) premixed with human transferrin (Tf) was used as a matrix, the signal intensity of insulin was amplified to more than ten times that of the respective control in CHCA without Tf. The detection limit of insulin was 0.39 fmol on-probe in the presence of Tf, while it was 6.3 fmol in the absence of Tf. The signal intensity of insulin was also enhanced when the CHCA matrix was premixed with proteins other than Tf (80 kDa), such as horse ferritin (20 kDa), bovine serum albumin (BSA, 66 kDa), or human immunoglobulin G (150 kDa). The optimum spectrum of insulin was obtained when the added amount of protein was in the range 0.26-0.62 pmol, regardless of the molecular weight of the added protein. Tf and BSA outperformed the other tested proteins, as determined by improvements in the resulting spectra. When the mass spectra of several peptides and proteins were recorded in the presence of Tf or BSA, the signal intensities of large peptides such as glucagon were enhanced, though those of smaller peptides were not enhanced. In addition, the signal enhancement achieved with Tf and BSA was more pronounced for the proteins, including cytochrome C, than for the large peptides. This enhancement effect could be applied to improve the sensitivity of MALDI-TOFMS to large peptides and proteins. Copyright 2004 John Wiley & Sons, Ltd.

  10. Multiple tube premixing device

    DOEpatents

    Uhm, Jong Ho; Naidu, Balachandar; Ziminksy, Willy Steve; Kraemer, Gilbert Otto; Yilmaz, Ertan; Lacy, Benjamin; Stevenson, Christian; Felling, David

    2013-08-13

    The present application provides a premixer for a combustor. The premixer may include a fuel plenum with a number of fuel tubes and a burner tube with a number of air tubes. The fuel tubes extend about the air tubes.

  11. Multiple tube premixing device

    DOEpatents

    Uhm, Jong Ho; Varatharajan, Balachandar; Ziminsky, Willy Steve; Kraemer, Gilbert Otto; Yilmaz, Ertan; Lacy, Benjamin; Stevenson, Christian; Felling, David

    2012-12-11

    The present application provides a premixer for a combustor. The premixer may include a fuel plenum with a number of fuel tubes and a burner tube with a number of air tubes. The fuel tubes extend about the air tubes.

  12. Studies in premixed combustion

    SciTech Connect

    Sivashinsky, G.I.

    1992-01-01

    This report discusses the following topics on premixed combustion: theory of turbulent flame propagation; pattern formation in premixed flames and related problems; and pattern formation in extended systems. (LSP)

  13. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue

    NASA Astrophysics Data System (ADS)

    Lee, Hyun Chul; Kim, Su-Jin; Kim, Kyung-Sup; Shin, Hang-Cheol; Yoon, Ji-Won

    2000-11-01

    A cure for diabetes has long been sought using several different approaches, including islet transplantation, regeneration of β cells and insulin gene therapy. However, permanent remission of type 1 diabetes has not yet been satisfactorily achieved. The development of type 1 diabetes results from the almost total destruction of insulin-producing pancreatic β cells by autoimmune responses specific to β cells. Standard insulin therapy may not maintain blood glucose concentrations within the relatively narrow range that occurs in the presence of normal pancreatic β cells. We used a recombinant adeno-associated virus (rAAV) that expresses a single-chain insulin analogue (SIA), which possesses biologically active insulin activity without enzymatic conversion, under the control of hepatocyte-specific L-type pyruvate kinase (LPK) promoter, which regulates SIA expression in response to blood glucose levels. Here we show that SIA produced from the gene construct rAAV-LPK-SIA caused remission of diabetes in streptozotocin-induced diabetic rats and autoimmune diabetic mice for a prolonged time without any apparent side effects. This new SIA gene therapy may have potential therapeutic value for the cure of autoimmune diabetes in humans.

  14. Insulin degludec, a long-acting once-daily basal analogue for type 1 and type 2 diabetes mellitus.

    PubMed

    Berard, Lori; MacNeill, Gail

    2015-02-01

    Here, we discuss certain practical issues related to use of insulin degludec, a new long-acting basal insulin analogue. Degludec provides uniform ("peakless") action that extends over more than 24 hours and is highly consistent from dose to dose. Like the 2 previously available basal analogues (detemir and glargine), degludec is expected to simplify dose adjustment and enable patients to reach their glycemic targets with reduced risk of hypoglycemia. Phase 3 clinical trials involving type 1 and type 2 diabetes have demonstrated that degludec was noninferior to glargine in allowing patients to reach a target glycated hemoglobin (A1C) of 7%, and nocturnal hypoglycemia occurred significantly less frequently with degludec. In addition, when dosing intervals vary substantially from day to day, degludec continues to be effective and to maintain a low rate of nocturnal hypoglycemia. Degludec thus has the potential to reduce risk of nocturnal hypoglycemia, to enhance the flexibility of the dosing schedule and to improve patient and caregiver confidence in the stability of glycemic control. A dedicated injector, the FlexTouch prefilled pen, containing degludec 200 units/mL, will be recommended for most patients with type 2 diabetes. Degludec will also be available as 100 units/mL cartridges, to be used in the NovoPen 4 by patients requiring smaller basal insulin doses, including most patients with type 1 diabetes.

  15. Type 1 diabetes control and pregnancy outcomes in women treated with continuous subcutaneous insulin infusion (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI).

    PubMed

    Bruttomesso, D; Bonomo, M; Costa, S; Dal Pos, M; Di Cianni, G; Pellicano, F; Vitacolonna, E; Dodesini, A R; Tonutti, L; Lapolla, A; Di Benedetto, A; Torlone, E

    2011-11-01

    The best way to treat pregnant patients who have type 1 diabetes is still unclear. For this reason, the present study compared metabolic control and maternal-fetal outcomes in patients treated with continuous subcutaneous infusions of rapid-acting insulin analogues (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI). This retrospective multicentre study involved 144 women with type 1 diabetes, 100 of whom were using CSII and 44 glargine-MDI. Outcomes analyzed were metabolic control, diabetes complications, pregnancy outcome, perinatal morbidity and mortality, and fetal malformations. The two groups were comparable for age, prepregnancy BMI, primiparous rate and diabetes complications, although patients using CSII had longer duration of diabetes (P=0.03) and higher White classifications (P=0.04). In both groups, metabolic control improved during pregnancy, but good control was reached earlier among patients using CSII. At parturition, patients using CSII had lower HbA(1c) (6.2±0.7% vs 6.5±0.8%; P=0.02) and required less insulin (P<0.01). Weight gain was similar in both groups, and maternal-fetal outcomes did not differ. In pregnant patients with type 1 diabetes, MDI and CSII are equivalent in terms of metabolic control and fetal-maternal outcomes, although patients using CSII achieved good control earlier and with less insulin. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  16. Simultaneous determination and validated quantification of human insulin and its synthetic analogues in human blood serum by immunoaffinity purification and liquid chromatography-mass spectrometry.

    PubMed

    Hess, Cornelius; Thomas, Andreas; Thevis, Mario; Stratmann, Bernd; Quester, Wulf; Tschoepe, Diethelm; Madea, Burkhard; Musshoff, Frank

    2012-10-01

    Possible fatal complications of human insulin and its synthetic analogues like hypoglycemia require precise classification and quantitative determination of these drugs both for clinical purposes as well as for forensic toxicologists. A procedure was developed for the identification and quantification of human insulin and different long-acting as well as short-acting synthetic insulins in human blood serum specimens. After an immunoaffinity purification step and separation by liquid chromatography, the insulins were characterized by their five- or sixfold protonated molecule ions and diagnostic product ions. Clinical samples of 207 diabetic and 50 non-diabetic patients after the administration of human insulin or oral antidiabetics and forensic samples were analyzed for human/synthetic insulin concentrations. The method was validated according to international guidelines. Limits of detection of the insulins ranged between 1.3 and 2.8 μU/ml. Recoveries ranged between 33.2 % and 51.7 %. Precision data was in accordance with international guidelines. Clinical samples showed concentrations of human insulin lower than 301 μU/ml. Our liquid chromatography tandem mass spectrometry procedure allows unambiguous identification and quantification of the intact human insulin and its intact synthetic analogues Humalog®, Novolog®, Apidra®, Lantus®, and Levemir® in human blood serum in clinical and overdose cases. The assay could be successfully tested in patients with diabetes mellitus on therapy with insulins or oral antidiabetics.

  17. Implications for the active form of human insulin based on the structural convergence of highly active hormone analogues

    PubMed Central

    Jiráček, Jiří; Žáková, Lenka; Antolíková, Emília; Watson, Christopher J.; Turkenburg, Johan P.; Dodson, Guy G.; Brzozowski, Andrzej M.

    2010-01-01

    Insulin is a key protein hormone that regulates blood glucose levels and, thus, has widespread impact on lipid and protein metabolism. Insulin action is manifested through binding of its monomeric form to the Insulin Receptor (IR). At present, however, our knowledge about the structural behavior of insulin is based upon inactive, multimeric, and storage-like states. The active monomeric structure, when in complex with the receptor, must be different as the residues crucial for the interactions are buried within the multimeric forms. Although the exact nature of the insulin’s induced-fit is unknown, there is strong evidence that the C-terminal part of the B-chain is a dynamic element in insulin activation and receptor binding. Here, we present the design and analysis of highly active (200–500%) insulin analogues that are truncated at residue 26 of the B-chain (B26). They show a structural convergence in the form of a new β-turn at B24-B26. We propose that the key element in insulin’s transition, from an inactive to an active state, may be the formation of the β-turn at B24-B26 associated with a trans to cis isomerisation at the B25-B26 peptide bond. Here, this turn is achieved with N-methylated L-amino acids adjacent to the trans to cis switch at the B25-B26 peptide bond or by the insertion of certain D-amino acids at B26. The resultant conformational changes unmask previously buried amino acids that are implicated in IR binding and provide structural details for new approaches in rational design of ligands effective in combating diabetes. PMID:20133841

  18. Dogfish glucagon analogues counter hyperglycaemia and enhance both insulin secretion and action in diet-induced obese diabetic mice.

    PubMed

    O'Harte, F P M; Ng, M T; Lynch, A M; Conlon, J M; Flatt, P R

    2016-10-01

    To investigate the antidiabetic actions of three dogfish glucagon peptide analogues [known glucagon-like peptide-1 and glucagon receptor co-agonists] after chronic administration in diet-induced high-fat-diet-fed diabetic mice. National Institutes of Health Swiss mice were pre-conditioned to a high-fat diet (45% fat) for 100 days, and control mice were fed a normal diet (10% fat). Normal diet control and high-fat-fed control mice received twice-daily intraperitoneal (i.p.) saline injections, while the high-fat-fed treatment groups (n = 8) received twice-daily injections of exendin-4(1-39), [S2a]dogfish glucagon, [S2a]dogfish glucagon exendin-4(31-39) or [S2a]dogfish glucagon-Lys(30) -γ-glutamyl-PAL (25 nmol/kg body weight) for 51 days. After dogfish glucagon analogue treatment, there was a rapid and sustained decrease in non-fasting blood glucose and an associated insulinotropic effect (analysis of variance, p < .05 to <.001) compared with saline-treated high-fat-fed controls. All peptide treatments significantly improved i.p. and oral glucose tolerance with concomitant increased insulin secretion compared with saline-treated high-fat-fed controls (p <.05 to <.001). After chronic treatment, no receptor desensitization was observed but insulin sensitivity was enhanced for all peptide-treated groups (p < .01 to <.001) except [S2a]dogfish glucagon. Both exendin-4 and [S2a]dogfish glucagon exendin-4(31-39) significantly reduced plasma triglyceride concentrations compared with those found in lean controls (p = .0105 and p = .0048, respectively). Pancreatic insulin content was not affected by peptide treatments but [S2a]dogfish glucagon and [S2a]dogfish glucagon exendin-4(31-39) decreased pancreatic glucagon by 28%-34% (p = .0221 and p = .0075, respectively). The percentage of β-cell area within islets was increased by exendin-4 and peptide analogue treatment groups compared with high-fat-fed controls and the β-cell area decreased

  19. Determination of human insulin and its analogues in human blood using liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS).

    PubMed

    Thomas, Andreas; Schänzer, Wilhelm; Thevis, Mario

    2014-01-01

    The qualitative and quantitative determination of insulin from human blood samples is an emerging topic in doping controls as well as in other related disciplines (e.g. forensics). Beside the therapeutic use, insulin represents a prohibited, performance enhancing substance in sports drug testing. In both cases accurate, sensitive, specific, and unambiguous determination of the target peptide is of the utmost importance. The challenges concerning identifying insulins in blood by liquid chromatography coupled to ion mobility mass spectrometry (LC-IM-MS) are detecting the basal concentrations of approximately 0.2 ng/mL and covering the hyperinsulinaemic clamps at > 3 ng/mL simultaneously using up to 200 μL of plasma or serum. This is achieved by immunoaffinity purification of the insulins with magnetic beads and subsequent separation by micro-scale liquid chromatography coupled to ion mobility / high resolution mass spectrometry. The method includes human insulin as well as the synthetic or animal analogues insulin aspart, glulisine, glargine, detemir, lispro, bovine, and porcine insulin. The method validation shows reliable results considering specificity, limit of detection (0.2 ng/mL except for detemir: 0.8 ng/mL), limit of quantification (0.5 ng/mL for human insulin), precision (CV < 20%), linearity (r > 0.99), recovery, accuracy (>90%), robustness (plasma/serum), and ion suppression. For quantification of human insulin a labelled internal standard ([[(2) H10 ]-Leu(B6,B11,B15,B17) ] - human Insulin) is introduced. By means of the additional ion mobility separation of the different analogues, the chromatographic run time is shortened to 8 min without losing specificity. As proof-of-concept, the procedure was successfully applied to different blood specimens from diabetic patients receiving recombinant synthetic analogues. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Macro- and microvascular outcomes in patients with type 2 diabetes treated with rapid-acting insulin analogues or human regular insulin: a retrospective database analysis.

    PubMed

    Rathmann, W; Schloot, N C; Kostev, K; Reaney, M; Zagar, A J; Haupt, A

    2014-02-01

    To investigate the risk of macro- and microvascular complications in patients with type 2 diabetes receiving rapid-acting insulin analogues (IA) or human regular insulin (HI).General practice diabetes patients with continuous prescription of any IA or HI for ≥3 years were selected from the German Disease Analyzer database (IMS Health). Logistic and Cox regression models were applied to analyze the incidence and time to onset of vascular outcomes (IA vs. HI).2764 patients on IA (insulin lispro, glulisine, aspart) and 4193 patients on HI were included (age, mean [SD]: 61.0 [11.3] and 64.7 [10.5] years, follow-up [Q1,Q3]: 4.6 [3.7,6.1] and 4.7 [3.7,5.9] years). No significant differences were detected between IA and HI regarding the incidence of vascular complications (OR [95%CI]: macrovascular 0.92 [0.72-1.18], microvascular 0.95 [0.77-1.17]) or regarding time to their onset, after adjustment for sex, age, comorbidities and time on IA/HI, or by propensity-score-based matching. However, in an additional short-term analysis (median [Q1,Q3] follow-up (IA 2.9 [1.2,4.6], HI 2.4 [0.8,4.4] years) of a larger sample (no continuous insulin treatment required) with more comorbidities, time to onset of macrovascular complications was significantly longer for AI than HI (HR 0.88 [0.81-0.97], p=0.009; microvascular complications: no difference).After long-term continuous treatment with IA or HI under real-life conditions, there was no different risk of macro- or microvascular complications, contradicting previous short-term analyses. Further prospective studies are needed to clarify whether selection bias may have been introduced by using strict entry criteria.

  1. Beraprost sodium, a stable prostacyclin analogue, improves insulin resistance in high-fat diet-induced obese mice.

    PubMed

    Inoue, Eriko; Ichiki, Toshihiro; Takeda, Kotaro; Matsuura, Hirohide; Hashimoto, Toru; Ikeda, Jiro; Kamiharaguchi, Aya; Sunagawa, Kenji

    2012-06-01

    Obesity induces hypertrophy of adipocyte resulting in production of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein 1 (MCP1 (CCL2)). These cytokines play an important role in the development of insulin resistance. Beraprost sodium (BPS), a prostaglandin I2 analogue, is reported to attenuate inflammation. In this study, we examined the effect of BPS on glucose metabolism in mice fed a high-fat diet (HFD). Four-week-old C57/B6 male mice were fed a HFD for 12 weeks (HFD group) and the treatment group received oral BPS (300 μg/kg per day) for the same period. Then, glucose metabolism, histological changes, and gene expression of white adipose tissue (WAT) were examined. Body weight was increased, and glucose intolerance and insulin resistance were developed in the HFD group. Treatment with BPS improved glucose tolerance and insulin action without body weight change. Histological analysis of WAT showed an increase in the size of adipocyte and macrophage infiltration in the HFD group, which was attenuated by BPS treatment. BPS reduced HFD-induced expression of MCP1 and TNF-α in WAT. BPS also attenuated hepatic steatosis induced by the HFD. These results suggest that BPS improved glucose intolerance possibly through suppression of inflammatory cytokines in WAT. BPS may be beneficial for the treatment of obesity-associated glucose intolerance.

  2. The exenatide analogue AC3174 attenuates hypertension, insulin resistance, and renal dysfunction in Dahl salt-sensitive rats.

    PubMed

    Liu, Que; Adams, Lisa; Broyde, Anatoly; Fernandez, Rayne; Baron, Alain D; Parkes, David G

    2010-08-03

    Activation of glucagon-like peptide-1 (GLP-1) receptors improves insulin sensitivity and induces vasodilatation and diuresis. AC3174 is a peptide analogue with pharmacologic properties similar to the GLP-1 receptor agonist, exenatide. Hypothetically, chronic AC3174 treatment could attenuate salt-induced hypertension, cardiac morbidity, insulin resistance, and renal dysfunction in Dahl salt-sensitive (DSS) rats. DSS rats were fed low salt (LS, 0.3% NaCl) or high salt (HS, 8% NaCl) diets. HS rats were treated with vehicle, AC3174 (1.7 pmol/kg/min), or GLP-1 (25 pmol/kg/min) for 4 weeks via subcutaneous infusion. Other HS rats received captopril (150 mg/kg/day) or AC3174 plus captopril. HS rat survival was improved by all treatments except GLP-1. Systolic blood pressure (SBP) was lower in LS rats and in GLP-1, AC3174, captopril, or AC3174 plus captopril HS rats than in vehicle HS rats (p < 0.05). AC3174 plus captopril attenuated the deleterious effects of high salt on posterior wall thickness, LV mass, and the ratio of LV mass to body weight (P < or = 0.05). In contrast, GLP-1 had no effect on these cardiovascular parameters. All treatments reduced LV wall stress. GLP-1, AC3174, captopril, or AC3174 plus captopril normalized fasting insulin and HOMA-IR (P < or = 0.05). AC3174, captopril, or AC3174 plus captopril improved renal function (P < or = 0.05). Renal morphology in HS rats was associated with extensive sclerosis. Monotherapy with AC3174, captopril, or GLP-1 attenuated renal damage. However, AC3174 plus captopril produced the most effective improvement. Thus, AC3174 had antihypertensive, cardioprotective, insulin-sensitizing, and renoprotective effects in the DSS hypertensive rat model. Furthermore, AC3174 improved animal survival, an effect not observed with GLP-1.

  3. Premixed conical flame stabilization

    NASA Astrophysics Data System (ADS)

    Krikunova, A. I.; Son, E. E.; Saveliev, A. S.

    2016-11-01

    In the current work, stabilization of premixed laminar and lean turbulent flames for wide range of flow rates and equivalence ratios was performed. Methane-air mixture was ignited after passing through premixed chamber with beads and grids, and conical nozzle (Bunsen-type burner). On the edge of the nozzle a stabilized body-ring was mounted. Ring geometry was varied to get the widest stable flame parameters. This work was performed as part of the project on experimental investigation of premixed flames under microgravity conditions.

  4. Qualitative determination of synthetic analogues of insulin in human plasma by immunoaffinity purification and liquid chromatography-tandem mass spectrometry for doping control purposes.

    PubMed

    Thevis, Mario; Thomas, Andreas; Delahaut, Philippe; Bosseloir, Alain; Schänzer, Wilhelm

    2005-06-01

    Synthetic insulins such as Humalog Lispro, Novolog Aspart, or Lantus Glargine, are commonly employed for the treatment of insulin-dependent diabetes mellitus owing to convenient handling and fast or prolonged bioavailability. However, the misuse of insulin in sports has been reported often, and the international doping control system requires a reliable and robust assay to determine the presence or absence of related drugs prohibited by the World Anti-Doping Agency. Qualitative evidence of administered substances, which is preferably obtained by mass spectrometry, is of utmost importance. Plasma specimens of 2 mL were fortified with three synthetic insulin analogues and purified by immunoaffinity chromatography, and extracts were analyzed by microbore liquid chromatography and tandem mass spectrometry. Product ion scan experiments of intact proteins enabled the differentiation between endogenously produced insulin and its synthetic analogues by collisionally activated dissociation of multiply charged precursor ions. This top-down sequencing-based assay allows the assignment of individual fragment ions, in particular, of those comprising modifications that are originating from C-termini of B-chains. Recoveries of synthetic insulins from plasma aliquots ranged from 91 to 98%, and detection limits were accomplished at 0.5 ng/mL for all target analytes.

  5. Gas turbine premixing systems

    SciTech Connect

    Kraemer, Gilbert Otto; Varatharajan, Balachandar; Evulet, Andrei Tristan; Yilmaz, Ertan; Lacy, Benjamin Paul

    2013-12-31

    Methods and systems are provided for premixing combustion fuel and air within gas turbines. In one embodiment, a combustor includes an upstream mixing panel configured to direct compressed air and combustion fuel through premixing zone to form a fuel-air mixture. The combustor includes a downstream mixing panel configured to mix additional combustion fuel with the fule-air mixture to form a combustion mixture.

  6. Insulin

    MedlinePlus

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  7. Premixed turbulent flame calculation

    NASA Technical Reports Server (NTRS)

    El-Tahry, S.; Rutland, C. J.; Ferziger, J. H.; Rogers, M. M.

    1987-01-01

    The importance of turbulent premixed flames in a variety of applications has led to a substantial amount of effort towards improving the understanding of these flames. Although these efforts have increased the understanding, many questions still remain. The use of direct numerical simulation (DNS) in solving these questions is examined.

  8. Premixed Turbulent Flame Propagation in Microgravity

    NASA Technical Reports Server (NTRS)

    Menon, S.; Disseau, M.; Chakravarthy, V. K.; Jagoda, J.

    1997-01-01

    Papers included address the following topics: (1) Turbulent premixed flame propagation in microgravity; (2) The effect of gravity on turbulent premixed flame propagation - a preliminary cold flow study; and (3) Characteristics of a subgrid model for turbulent premixed combustion.

  9. Premixed direct injection nozzle

    DOEpatents

    Zuo, Baifang [Simpsonville, SC; Johnson, Thomas Edward [Greer, SC; Lacy, Benjamin Paul [Greer, SC; Ziminsky, Willy Steve [Simpsonville, SC

    2011-02-15

    An injection nozzle having a main body portion with an outer peripheral wall is disclosed. The nozzle includes a plurality of fuel/air mixing tubes disposed within the main body portion and a fuel flow passage fluidly connected to the plurality of fuel/air mixing tubes. Fuel and air are partially premixed inside the plurality of the tubes. A second body portion, having an outer peripheral wall extending between a first end and an opposite second end, is connected to the main body portion. The partially premixed fuel and air mixture from the first body portion gets further mixed inside the second body portion. The second body portion converges from the first end toward said second end. The second body portion also includes cooling passages that extend along all the walls around the second body to provide thermal damage resistance for occasional flame flash back into the second body.

  10. Brevinin-2-related peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet.

    PubMed

    Abdel-Wahab, Y H A; Patterson, S; Flatt, P R; Conlon, J M

    2010-08-01

    The cationic, alpha-helical frog skin antimicrobial peptide B2RP (brevinin-2-related peptide) shows sequence similarity to antimicrobial peptides belonging to the brevinin-2 family, but lacks the C-terminal cyclic heptapeptide domain (Cys-Lys-Xaa (4)-Cys). Synthetic B2RP produced a significant (p<0.05) stimulation of insulin release (148% of basal rate at a concentration of 1 muM with a maximum response of 222% of basal rate at a concentration of 3 muM) from BRIN-BD11 clonal beta-cells without increasing the release of the cytosolic enzyme, lactate dehydrogenase. Increasing cationicity of B2RP while maintaining amphipathicity by the substitution Asp (4) --> Lys enhanced the insulin-releasing potency (137% of basal rate at a concentration of 0.3 muM; p<0.05) with no stimulation of lactate dehydrogenase release. In contrast, the L18K, and D4K, L18K analogues were toxic to the cells, and the K16A analogue, with increased amphipathicity and hydrophobicity, showed reduced potency. Administration of [D4K]B2RP (100 nmol/kg body weight) to mice fed a high fat diet to induce obesity and insulin-resistance significantly (p<0.05) enhanced insulin release and improved glucose tolerance during the 60-minute period following an intraperitoneal glucose load (18 mmol/kg body weight). B2RP shows potential for development into an agent for the treatment of type 2 diabetes.

  11. Novel GLP-1 (Glucagon-Like Peptide-1) Analogues and Insulin in the Treatment for Alzheimer's Disease and Other Neurodegenerative Diseases.

    PubMed

    Calsolaro, Valeria; Edison, Paul

    2015-12-01

    The link between diabetes mellitus and Alzheimer's disease (AD) has been known for the last few decades. Since insulin and insulin receptors are known to be present in the brain, the downstream signalling as well as the effect of hyperinsulinemia have been extensively studied in both AD and Parkinson's disease. Glucagon-like peptide-1 (GLP-1) is a hormone belonging to the incretin family, and its receptors (GLP-1Rs) can be found in pancreatic cells and in vascular endothelium. Interestingly, GLP-1Rs are found in the neuronal cell body and dendrites in the central nervous system (CNS), in particular in the hypothalamus, hippocampus, cerebral cortex and olfactory bulb. Several studies have shown the importance of both insulin and GLP-1 signalling on cognitive function, and many preclinical studies have been performed to evaluate the potential protective role of GLP-1 on the brain. Here we review the underlying mechanism of insulin and GLP-1 signalling in the CNS, as well as the preclinical data for the use of GLP-1 analogues such as liraglutide, exenatide and lixisenatide in neurodegenerative diseases.

  12. Total Chemical Synthesis of a Heterodimeric Interchain Bis-Lactam-Linked Peptide: Application to an Analogue of Human Insulin-Like Peptide 3

    PubMed Central

    Karas, John; Shabanpoor, Fazel; Hossain, Mohammed Akhter; Wade, John D.; Scanlon, Denis B.

    2013-01-01

    Nonreducible cystine isosteres represent important peptide design elements in that they can maintain a near-native tertiary conformation of the peptide while simultaneously extending the in vitro and in vivo half-life of the biomolecule. Examples of these cystine mimics include dicarba, diselenide, thioether, triazole, and lactam bridges. Each has unique physicochemical properties that impact upon the resulting peptide conformation. Each also requires specific conditions for its formation via chemical peptide synthesis protocols. While the preparation of peptides containing two lactam bonds within a peptide is technically possible and reported by others, to date there has been no report of the chemical synthesis of a heterodimeric peptide linked by two lactam bonds. To examine the feasibility of such an assembly, judicious use of a complementary combination of amine and acid protecting groups together with nonfragment-based, total stepwise solid phase peptide synthesis led to the successful preparation of an analogue of the model peptide, insulin-like peptide 3 (INSL3), in which both of the interchain disulfide bonds were replaced with a lactam bond. An analogue containing a single disulfide-substituted interchain lactam bond was also prepared. Both INSL3 analogues retained significant cognate RXFP2 receptor binding affinity. PMID:24288548

  13. Effect of a β-Hydroxyphosphonate Analogue of ʟ-Carnitine on Insulin-Sensitive and Insulin-Resistant 3T3-L1 Adipocytes.

    PubMed

    Avalos-Soriano, Anaguiven; De la Cruz-Cordero, Ricardo; López-Martínez, Francisco Josue; Rosado, Jorge L; Duarte-Vázquez, Miguel Ángel; Garcia-Gasca, Teresa

    2015-01-01

    This study investigated the effect of a β-x200B;hydroxyphosphonate analog of ʟ-carnitine (L-CA) (CAS number: 1220955-x200B;20-3, Component: 1221068-91-2, C12H29NO4PI), (3-Hexanaminium, 1-(dimethoxyphosphinyl)-2-hydroxy-N,N,N,5-x200B;tetramethy-iodide (1:1), (2R, 3S)) on parameters related with type-2 diabetes in an in vitro model. Nontoxic concentrations of L-CA were assayed and compared to commercial ʟ-carnitine effects. L-CA did not affect adipogenesis in normal cells, but an increment of TG accumulation was observed on insulin-resistant adipocytes (80%) when compared with resistant control. L-CA also stimulated glucose analog 2-NBDG uptakes on insulin-resistant adipocytes in a similar way as insulin when compared to insulin-resistant cells. Our results show that the L-CA promoted insulin-like responses on insulin-resistant adipocytes without appreciable pro-adipogenic effect in sensitive adipocytes. © 2015 S. Karger AG, Basel.

  14. Characteristics Predictive for a Successful Switch from Insulin Analogue Therapy to Oral Hypoglycemic Agents in Patients with Type 2 Diabetes

    PubMed Central

    Kim, Gyuri; Lee, Yong-ho; Kang, Eun Seok; Cha, Bong-Soo; Lee, Hyun Chul

    2016-01-01

    Purpose The objective of this study was to investigate clinical and laboratory parameters that could predict which patients could maintain adequate glycemic control after switching from initial insulin therapy to oral hypoglycemic agents (OHAs) among patients with type 2 diabetes (T2D). Materials and Methods We recruited 275 patients with T2D who had been registered in 3 cohorts of initiated insulin therapy and followed up for 33 months. The participants were divided into 2 groups according to whether they switched from insulin to OHAs (Group I) or not (Group II), and Group I was further classified into 2 sub-groups: maintenance on OHAs (Group IA) or resumption of insulin (Group IB). Results Of 275 patients with insulin initiation, 63% switched to OHAs (Group I) and 37% continued insulin (Group II). Of these, 44% were in Group IA and 19% in Group IB. The lowest tertile of baseline postprandial C-peptide-to-glucose ratio (PCGR), higher insulin dose at switching to OHAs, and higher HbA1c level at 6 months after switching to OHAs were all associated with OHA failure (Group IB; p=0.001, 0.046, and 0.014, respectively). The lowest tertile of PCGR was associated with ultimate use of insulin (Group IB and Group II; p=0.029). Conclusion Higher baseline level of PCGR and lower HbA1c levels at 6 months after switching to OHAs may be strong predictors for the successful maintenance of OHAs after switching from insulin therapy in Korean patients with T2D. PMID:27593867

  15. Novel dual agonist peptide analogues derived from dogfish glucagon show promising in vitro insulin releasing actions and antihyperglycaemic activity in mice.

    PubMed

    O'Harte, F P M; Ng, M T; Lynch, A M; Conlon, J M; Flatt, P R

    2016-08-15

    The antidiabetic potential of thirteen novel dogfish glucagon derived analogues were assessed in vitro and in acute in vivo studies. Stable peptide analogues enhanced insulin secretion from BRIN-BD11 β-cells (p < 0.001) and reduced acute glycaemic responses following intraperitoneal glucose (25 nmol/kg) in healthy NIH Swiss mice (p < 0.05-p<0.001). The in vitro insulinotropic actions of [S2a]dogfish glucagon, [S2a]dogfish glucagon-exendin-4(31-39) and [S2a]dogfish glucagon-Lys(30)-γ-glutamyl-PAL, were blocked (p < 0.05-p<0.001) by the specific GLP-1 and glucagon receptor antagonists, exendin-4(9-39) and (desHis(1)Pro(4)Glu(9))glucagon amide but not by (Pro(3))GIP, indicating lack of GIP receptor involvement. These analogues dose-dependently stimulated cAMP production in GLP-1 and glucagon (p < 0.05-p<0.001) but not GIP-receptor transfected cells. They improved acute glycaemic and insulinotropic responses in high-fat fed diabetic mice and in wild-type C57BL/6J and GIPR-KO mice (p < 0.05-p<0.001), but not GLP-1R-KO mice, confirming action on GLP-1 but not GIP receptors. Overall, dogfish glucagon analogues have potential for diabetes therapy, exerting beneficial metabolic effects via GLP-1 and glucagon receptors. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Effect of one year continuous subcutaneous infusion of a somatostatin analogue, octreotide, on early retinopathy, metabolic control and thyroid function in Type I (insulin-dependent) diabetes mellitus.

    PubMed

    Kirkegaard, C; Nørgaard, K; Snorgaard, O; Bek, T; Larsen, M; Lund-Andersen, H

    1990-06-01

    Growth hormone is assumed to be involved in the development of diabetic retinopathy. In a randomized study we evaluated the possible effects of one year treatment with a somatostatin (SRIH) analogue, octreotide, on early retinopathy and on metabolism in Type I (insulin-dependent) diabetes mellitus. Eleven patients were allocated to treatment with a continuous sc infusion of 400 micrograms octreotide per day and 9 served as controls. Only 7 patients from each group completed the study. Three octreotide-treated patients left the study owing to severe diarrhea. The subjects were evaluated at entry, after 2, 6 and 12 months treatment, and 2 months after withdrawal. Octreotide induced a decrease in GH secretion, expressed as the area under the 24 h serum GH profiles (p less than 0.05), and of the serum levels of IGF-I (p less than 0.05). The entire decline in GH levels occurred during the daytime, whereas the nocturnal levels were unaffected. Retinopathy, as assessed by determination of the blood retina barrier permeability, by colour fundus photography, and flurescein angiography was unchanged in both groups. Apart from a decline in insulin requirements, octreotide had no major effect on glycemic control, but induced a mild transient pituitary hypothyroidism, not clinically relevant. We conclude that treatment with octreotide for one year has modest effects on GH, IGF-I, and glucose metabolism, but has no significant effect on early retinopathy in Type I (insulin-dependent) diabetes.

  17. The effects of GLP-1 analogues in obese, insulin-using type 2 diabetes in relation to eating behaviour.

    PubMed

    de Boer, Stefanie Amarens; Lefrandt, Joop Daniel; Petersen, Japke Frida; Boersma, Hendrikus Hessel; Mulder, Douwe Johannes; Hoogenberg, Klaas

    2016-02-01

    Glucagon-like peptide-1 receptor agonists (GLP-1 RA) added to insulin in type 2 diabetes patients have shown to lower body weight, improve glycaemic control and reduce total daily insulin dose in short term studies, although the individual response greatly varies. To evaluate GLP-1 RA treatment on body weight, glycaemic control and total daily insulin dose in obese, insulin-using type 2 diabetes patients after 2 years follow-up in a real life setting and to explore a possible relation with eating behaviour. The Martini Hospital and the University Medical Center in Groningen in the Netherlands. Eligible patients were at least 18 years of age, were on insulin therapy and obese (BMI > 30 kg/m(2)), started GLP-1 RA treatment. At baseline eating behaviour was classified according to the validated Dutch Eating Behaviour Questionnaire. A 2 years follow-up was performed. Main outcome measures Body weight, HbA1c and total daily insulin dose. 151 Patients started with exenatide or liraglutide. 120 patients completed the 2 years follow-up. From baseline to 2 years, body weight (mean ± SD) changed from 117.9 ± 22.1 to 107.9 ± 22.9 kg (P < 0.0001), HbA1c (median, IQR) changed from 7.9 (7.2-8.9) to 7.6 (6.9-8.3) % [63 (55-74) to 60 (52-67) mmol/mol] (P < 0.0001), total daily insulin dose changed from 90 (56-150) to 60 (0-100) Units/day (P < 0.0001). Weight change differed between eating behaviour groups (P < 0.001) in which external eating behaviour (n = 17) resulted in the smallest decline (-3.1 %) and restrained (n = 41) in the greatest (-10.3 %) in comparison with emotional (n = 37, -8.5 %) and indifferent (n = 25, -9.6 %) eating behaviours. Two year of GLP-1 RA treatment resulted in a sustained reduction of weight, HbA1c and total daily insulin dose in obese, insulin-using type 2 diabetes patients in a real life setting. Largest weight loss was achieved in patients with a predominant restraint eating pattern while a predominant external eating pattern resulted in the

  18. Insulin

    NASA Technical Reports Server (NTRS)

    2004-01-01

    The manipulation of organic materials--cells, tissues, and even living organisms--offers many exciting possibilities for the future from organic computers to improved aquaculture. Commercial researchers are using the microgravity environment to produce large near perfect protein crystals Research on insulin has yielded crystals that far surpass the quality of insulin crystals grown on the ground. Using these crystals industry partners are working to develop new and improved treatments for diabetes. Other researchers are exploring the possibility of producing antibiotics using plant cell cultures which could lead to both orbital production and the improvement of ground-based antibiotic production.

  19. Premixed direct injection disk

    SciTech Connect

    York, William David; Ziminsky, Willy Steve; Johnson, Thomas Edward; Lacy, Benjamin; Zuo, Baifang; Uhm, Jong Ho

    2013-04-23

    A fuel/air mixing disk for use in a fuel/air mixing combustor assembly is provided. The disk includes a first face, a second face, and at least one fuel plenum disposed therebetween. A plurality of fuel/air mixing tubes extend through the pre-mixing disk, each mixing tube including an outer tube wall extending axially along a tube axis and in fluid communication with the at least one fuel plenum. At least a portion of the plurality of fuel/air mixing tubes further includes at least one fuel injection hole have a fuel injection hole diameter extending through said outer tube wall, the fuel injection hole having an injection angle relative to the tube axis. The invention provides good fuel air mixing with low combustion generated NOx and low flow pressure loss translating to a high gas turbine efficiency, that is durable, and resistant to flame holding and flash back.

  20. Lean premixed/prevaporized combustion

    NASA Technical Reports Server (NTRS)

    Lefebvre, A. H. (Editor)

    1977-01-01

    Recommendations were formulated on the status and application of lean premixed/prevaporized combustion to the aircraft gas turbine for the reduction of pollutant emissions. The approach taken by the NASA Stratospheric Cruise Emission Reduction Program (SCERP) in pursuing the lean premixed/prevaporized combustion technique was also discussed. The proceedings contains an overview of the SCERP program, the discussions and recommendations of the participants, and an overall summary.

  1. Subject-driven titration of biphasic insulin aspart 30 twice daily is non-inferior to investigator-driven titration in Chinese patients with type 2 diabetes inadequately controlled with premixed human insulin: A randomized, open-label, parallel-group, multicenter trial.

    PubMed

    Yang, Wenying; Zhu, Lvyun; Meng, Bangzhu; Liu, Yu; Wang, Wenhui; Ye, Shandong; Sun, Li; Miao, Heng; Guo, Lian; Wang, Zhanjian; Lv, Xiaofeng; Li, Quanmin; Ji, Qiuhe; Zhao, Weigang; Yang, Gangyi

    2016-01-01

    The present study was to compare the efficacy and safety of subject-driven and investigator-driven titration of biphasic insulin aspart 30 (BIAsp 30) twice daily (BID). In this 20-week, randomized, open-label, two-group parallel, multicenter trial, Chinese patients with type 2 diabetes inadequately controlled by premixed/self-mixed human insulin were randomized 1:1 to subject-driven or investigator-driven titration of BIAsp 30 BID, in combination with metformin and/or α-glucosidase inhibitors. Dose adjustment was decided by patients in the subject-driven group after training, and by investigators in the investigator-driven group. Eligible adults (n = 344) were randomized in the study. The estimated glycated hemoglobin (HbA1c) reduction was 14.5 mmol/mol (1.33%) in the subject-driven group and 14.3 mmol/mol (1.31%) in the investigator-driven group. Non-inferiority of subject-titration vs investigator-titration in reducing HbA1c was confirmed, with estimated treatment difference -0.26 mmol/mol (95% confidence interval -2.05, 1.53) (-0.02%, 95% confidence interval -0.19, 0.14). Fasting plasma glucose, postprandial glucose increment and self-measured plasma glucose were improved in both groups without statistically significant differences. One severe hypoglycemic event was experienced by one subject in each group. A similar rate of nocturnal hypoglycemia (events/patient-year) was reported in the subject-driven (1.10) and investigator-driven (1.32) groups. There were 64.5 and 58.1% patients achieving HbA1c <53.0 mmol/mol (7.0%), and 51.2 and 45.9% patients achieving the HbA1c target without confirmed hypoglycemia throughout the trial in the subject-driven and investigator-driven groups, respectively. Subject-titration of BIAsp 30 BID was as efficacious and well-tolerated as investigator-titration. The present study supported patients to self-titrate BIAsp 30 BID under physicians' supervision.

  2. [Adherence of type 2 diabetes patients on insulin analogues application: missed dose, time imprecision and dose reduction. The results of GAPP2TM(Global Attitudes of Physicians and Patient) survey in the Czech Republic].

    PubMed

    Prázný, Martin

    2014-11-01

    Irregular insulin dose is one of the main problems associated with insulin therapy in patients with type 2 diabetes; its extent is not known precisely. The aim of survey conducted in the Czech Republic in the international project GAPP2 - Global Attitudes of Patients and Physicians was to determine the incidence and the impact of irregular use of basal insulin analogues in patients with type 2 diabetes, to point out the reasons for these irregularities and to focus on how physicians discuss irregular application of insulin with patients. The project GAPP2 is an international cross-sectional study performed on-line via the Internet using a questionnaire filled by diabetic patients treated with insulin analogues and physicians who treat these patients. The survey was conducted in two steps in 17 countries; the first step included 6 countries and was completed in the beginning of 2012, the second step involved 11 other countries including the Czech Republic with termination in 2014. The survey was designed to obtain the views of patients and physicians on certain aspects of insulin treatment and persistent issues in this field in the real daily practice. Special focus was on the incidence and management of hypoglycaemia as well as on irregularities of insulin application. In the part dedicated to adherence to basal insulin application were observed three types of irregular insulin therapy: missed dose, time imprecision of dose (± 2 hours vs. the prescribed time) and dose reduction in all cases in the past 30 days before completing the questionnaire. In addition, it was investigated the attitude and relation of patients to these issues. The results have shown that irregular insulin dose in the Czech Republic is less frequent than in other countries involved in the GAPP2 research. Nevertheless, approximately one fifth of diabetic patients using insulin analogues in basal-bolus or only basal therapy regimen is related to this problem. The last irregular insulin

  3. [INITIATING AND INTENSIFYING INSULIN THERAPY IN GENERAL PRACTICE: INSUSTAR, AN OBSERVATIONAL BELGIAN PROSPECTIVE STUDY IN TYPE 2 DIABETES].

    PubMed

    Scheen, A J; Mathieu, C; Nobels, F

    2015-09-01

    Initiating or intensifying insulin therapy is often considered as a challenge in general practice. The observational prospective Belgian study InsuStar was performed in 2011-2013 among 150 representative general practitioners, who were invited to initiate or intensify insulin therapy when necessary in 523 patients with type 2 diabetes (mean age: 65.5 years; mean HbAk: 8.8%). The initiation of insulin therapy (glargine in > 50%) was justified by insufficient glycaemic control (96%) and its intensification (replacement of insulin NPH or premixed insulins by insulin glargine, eventually with the addition of a short-acting insulin analogue) aimed at improving glucose control (58%), avoiding hypoglycaemia (17%) or both (17%). After a follow up of 6:1 months, HbAlc level decreased from 8.79% to 7.52% (-1.27%; 95% confidence interval: -1.43, -1.11; p<0.001). Overall 27.6% of patients reached an HbAl, < 7% versus 5.9% at inclusion (p<0.001), with rather few hypoglycaemia and a high physi- cian confidence level regarding insulin therapy. These results should encourage general practitioners to initiate insulin therapy at an earlier stage and to intensify it when necessary in patients with insufficiently controlled type 2 diabetes.

  4. High-mix insulins

    PubMed Central

    Kalra, Sanjay; Farooqi, Mohammad Hamed; El-Houni, Ali E.

    2015-01-01

    Premix insulins are commonly used insulin preparations, which are available in varying ratios of different molecules. These drugs contain one short- or rapid-acting, and one intermediate- or long-acting insulin. High-mix insulins are mixtures of insulins that contain 50% or more than 50% of short-acting insulin. This review describes the clinical pharmacology of high-mix insulins, including data from randomized controlled trials. It suggests various ways, in which high-mix insulin can be used, including once daily, twice daily, thrice daily, hetero-mix, and reverse regimes. The authors provide a rational framework to help diabetes care professionals, identify indications for pragmatic high-mix use. PMID:26425485

  5. Premixed Prevaporized Combustor Technology Forum

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The Forum was held to present the results of recent and current work intended to provide basic information required for demonstration of lean, premixed prevaporized combustors for aircraft gas turbine engine application. Papers are presented which deal with the following major topics: (1) engine interfaces; (2) fuel-air preparation; (3) autoignition; (4) lean combustion; and (5) concept design studies.

  6. Statistics of premixed flame cells

    SciTech Connect

    Noever, D.A. )

    1991-07-15

    The statistics of random cellular patterns in premixed flames are analyzed. Agreement is found with a variety of topological relations previously found for other networks, namely, Lewis's law and Aboav's law. Despite the diverse underlying physics, flame cells are shown to share a broad class of geometric properties with other random networks---metal grains, soap foams, bioconvection, and Langmuir monolayers.

  7. Statistics of premixed flame cells

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1991-01-01

    The statistics of random cellular patterns in premixed flames are analyzed. Agreement is found with a variety of topological relations previously found for other networks, namely, Lewis's law and Aboav's law. Despite the diverse underlying physics, flame cells are shown to share a broad class of geometric properties with other random networks-metal grains, soap foams, bioconvection, and Langmuir monolayers.

  8. Statistics of premixed flame cells

    NASA Technical Reports Server (NTRS)

    Noever, David A.

    1991-01-01

    The statistics of random cellular patterns in premixed flames are analyzed. Agreement is found with a variety of topological relations previously found for other networks, namely, Lewis's law and Aboav's law. Despite the diverse underlying physics, flame cells are shown to share a broad class of geometric properties with other random networks-metal grains, soap foams, bioconvection, and Langmuir monolayers.

  9. Insulin therapy in type 2 diabetes.

    PubMed

    Mudaliar, S; Edelman, S V

    2001-12-01

    Type 2 diabetes is a common disorder often accompanied by numerous metabolic abnormalities leading to a high risk of cardiovascular morbidity and mortality. Results from the UKPDS have confirmed that intensive glucose control delays the onset and retards the progression of microvascular disease and possibly of macrovascular disease in patients with type 2 diabetes. In the early stages of the disease, insulin resistance plays a major role in the development of hyperglycemia and other metabolic abnormalities, and patients with type 2 diabetes often benefit from measures to improve insulin sensitivity such as weight loss, dietary changes, and exercise. Later, the use of oral insulin secretagogues and insulin sensitizers as monotherapy and in combination helps maintain glycemia for varying periods of time. Ultimately, because of the progressive nature of the disease and the progressive decline in pancreatic beta-cell function, insulin therapy is almost always obligatory to achieve optimal glycemic goals. Not all patients are candidates for aggressive insulin management; therefore, the goals of therapy should be modified, especially in elderly individuals and those with co-morbid conditions. Candidates for intensive management should be motivated, compliant, and educable, without other major medical conditions and physical limitations that would preclude accurate and reliable HGM and insulin administration. In selected patients, combination therapy with insulin and oral antidiabetic medications can be an effective method for normalizing glycemia without the need for rigorous multiple-injection regimens. The patients for whom combination therapy is most commonly successful are those who do not achieve adequate glycemic control using daytime oral agents but who still show some evidence of responsiveness to the medications. Bedtime intermediate-acting or predinner premixed intermediate- and rapid-acting insulin is administered and progressively increased until the FPG

  10. Insulin release and phosphate ion efflux from rat pancreatic islets induced by L-leucine and its nonmetabolizable analogue, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid.

    PubMed Central

    Freinkel, N; Younsi, C E; Dawson, R M

    1976-01-01

    When isolated rat pancreatic islets that had been labeled with 32P were exposed to 10mM L-leucine in a microperifusion system, there was a transitory, immediate heightened efflux of [32P]phosphate ions. Commencement of the phosphate flush coincided with the first release of insulin, and it occurred in the absence or presence of nonstimulatory levels of glucose (0.5 mg/ml). The effects of leucine upon phosphate efflux were not inhibited by D-mannoheptulose, whereas glucose-induced stimulations were suppressed. The phosphate flush could be induced also by the nonmetabolizable analogue of leucine, 2-aminobicyclo[2.2.1]heptane-2-carboxylic acid. Like insulin release, the effect was stereospecific, with only one of the four stereoisomers, (-)-b-aminobicycloheptane carboxylic acid, being active. Analogue-induced phosphate and insulin release were totally suppressed in a medium containing D2O, but on reversion to H2O the efflux of both hormone and anion occured. It is concluded that insulin secretion from islet beta cells and the release of phosphate ions showed the same specificity for nutrient secretagogues and that both can be triggered even in the absence of exogenous oxidizable fuels. However, the partial dissociation of the dose-response curves for the two phenomena lends support to the contention that the phosphate flush reflects an earlier event in the sequence of stimulus-secretion coupling. PMID:790384

  11. [Mild hypoglycaemia is common in type 2 diabetic patients treated with insulin analogues in the Czech Republic and the patients are concerned about it: results of a GAPP2TM survey (Global Attitudes of Physicians and Patient)].

    PubMed

    Prázný, Martin

    2015-03-01

    Mild hypoglycaemia affects diabetes management, productivity and quality of life of patients. Data are scarce about the incidence of mild hypoglycaemia in daily life of type 2 diabetic patients treated with insulin analogues. The aim was to focus on the incidence of mild hypoglycaemia and its consequences in the international GAPP2 survey (Global Attitudes of Patient and Physicians) conducted also in the Czech Republic. The GAPP2 project - Global Attitudes of Patients and Physicians is an international cross-sectional study conducted online via Internet in a questionnaire form dedicated to type 2 diabetic patients treated with insulin analogues and physicians who treat these patients. The survey was realized in two steps including 17 countries. The first step was completed by six countries in 2012. The second step was terminated by additional eleven countries including the Czech Republic in 2014. The survey was designed to obtain data on some aspects of insulin therapy and persistent issues in daily practice from the views of patients and physicians. One part of survey was dedicated to mild hypoglycaemia occurring in treatment with insulin analogues. The incidence of mild hypoglycaemia and the reaction of patients and physicians on hypoglycaemia (including modification of therapy, self-monitoring) were investigated. Moreover, there was investigated the impact of mild hypoglycaemia on quality of life from the view of patients and physicians. The results of the survey have shown that mild hypoglycaemia is common in patients with insulin analogues in the Czech Republic. In addition, patients in the Czech Republic are more afraid from hypoglycaemia and feel more limited in daily life in comparison to other countries in GAPP2 survey. Patients try to avoid nocturnal hypoglycaemia through reduction or omission of prescribed dose of insulin. Furthermore, research has observed that physicians are poorly informed by patients about incidence and severity of hypoglycaemia. The

  12. Clinical use of the co-formulation of insulin degludec and insulin aspart.

    PubMed

    Kumar, A; Awata, T; Bain, S C; Ceriello, A; Fulcher, G R; Unnikrishnan, A G; Arechavaleta, R; Gonzalez-Gálvez, G; Hirose, T; Home, P D; Kaku, K; Litwak, L; Madsbad, S; Pinget, M; Mehta, R; Mithal, A; Tambascia, M; Tibaldi, J; Christiansen, J S

    2016-08-01

    To provide a review of the available data and practical use of insulin degludec with insulin aspart (IDegAsp). Premixed insulins provide basal and prandial glucose control; however, they have an intermediate-acting prandial insulin component and do not provide as effective basal coverage as true long-acting insulins, owing to the physicochemical incompatibility of their individual components, coupled with the inflexibility of adjustment. The molecular structure of the co-formulation of IDegAsp, a novel insulin preparation, allows these two molecules to coexist without affecting their individual pharmacodynamic profiles. Clinical evidence in phase 2/3 trials of IDegAsp efficacy and safety in type 1 and type 2 diabetes mellitus (T1DM and T2DM) have been assessed and summarised. In people with T2DM, once- and twice-daily dosing provides similar overall glycaemic control (HbA1c ) to current modern insulins, but with lower risk of nocturnal hypoglycaemia. In prior insulin users, glycaemic control was achieved with lower or equal insulin doses vs. other basal+meal-time or premix insulin regimens. In insulin-naïve patients with T2DM, IDegAsp can be started once or twice-daily, based on individual need. People switching from more than once-daily basal or premix insulin therapy can be converted unit-to-unit to once-daily IDegAsp, although this strategy should be assessed by the physician on an individual basis. IDegAsp offers physicians and people with T2DM a simpler insulin regimen than other available basal-bolus or premix-based insulin regimens, with stable daytime basal coverage, a lower rate of hypoglycaemia and some flexibility in injection timing compared with premix insulins. © 2016 John Wiley & Sons Ltd.

  13. Turbulent transport in premixed flames

    NASA Technical Reports Server (NTRS)

    Rutland, C. J.; Cant, R. S.

    1994-01-01

    Simulations of planar, premixed turbulent flames with heat release were used to study turbulent transport. Reynolds stress and Reynolds flux budgets were obtained and used to guide the investigation of important physical effects. Essentially all pressure terms in the transport equations were found to be significant. In the Reynolds flux equations, these terms are the major source of counter-gradient transport. Viscous and molecular terms were also found to be significant, with both dilatational and solenoidal terms contributing to the Reynolds stress dissipation. The BML theory of premixed turbulent combustion was critically examined in detail. The BML bimodal pdf was found to agree well with the DNS data. All BML decompositions, through the third moments, show very good agreement with the DNS results. Several BML models for conditional terms were checked using the DNS data and were found to require more extensive development.

  14. Lewis Number Effects on Partially Premixed Flames

    NASA Technical Reports Server (NTRS)

    Ruetsch, G. R.; Ferziger, J.

    1996-01-01

    Combustion is generally categorized as either premixed, where flames propagate into homogeneous mixtures of reactants, or as nonpremixed, where initially separated reactants diffuse into the reaction zones. Although these approaches are applicable to many combustion devices, there are cases not in either of these two limiting regimes. Under such circumstances, one must consider partially premixed combustion. In partially premixed combustion, mechanisms from both premixed and nonpremixed regimes coexist and, as a result, some interesting phenomena arise. One such phenomenon is flame stabilization in laminar mixing layers by triple flames.

  15. Premixed Parenteral Nutrition Solution Use in Children

    PubMed Central

    Crill, Catherine M.

    2015-01-01

    OBJECTIVES: In response to national drug shortages, our institution established criteria for the use of commercial premixed parenteral nutrition (PN) solutions in select pediatric patients. Although these solutions have been marketed for use in children, there are no data in this patient population. The objective of this study was to review our use of commercial premixed PN solutions in children. METHODS: This was a retrospective review of patients ≤18 years of age who received a premixed PN solution from October 2010 to April 2012. All premixed PN courses were assessed for incidence of premixed PN discontinuation due to laboratory abnormalities. Estimated goal and actual protein and total caloric intake were evaluated for premixed PN courses that were continued for >48 hours. RESULTS: Sixty-nine patients received 74 courses of premixed PN solutions for a mean duration of 5.6 ± 6.2 (range, 1–31) days. Fifteen courses (20%) required discontinuation of premixed PN as a result of mild laboratory abnormalities. No changes in clinical status were observed in patients and all abnormalities were corrected after switching to individualized PN. In patients receiving PN for >48 hours, premixed PN solutions provided goal protein in 48/49 (98%) courses and goal calories in 33/49 (67%) courses. CONCLUSIONS: Premixed PN solutions were used in a wide range of pediatric patients and provide a potential option for PN support in pediatric patients when drug shortages limit PN product supply. Close monitoring for electrolyte abnormalities and protein and caloric intake is recommended when using premixed PN solutions in children. PMID:26472952

  16. Gas turbine premixer with internal cooling

    DOEpatents

    York, William David; Johnson, Thomas Edward; Lacy, Benjamin Paul; Stevenson, Christian Xavier

    2012-12-18

    A system that includes a turbine fuel nozzle comprising an air-fuel premixer. The air-fuel premixed includes a swirl vane configured to swirl fuel and air in a downstream direction, wherein the swirl vane comprises an internal coolant path from a downstream end portion in an upstream direction through a substantial length of the swirl vane.

  17. Flashback resistant pre-mixer assembly

    DOEpatents

    Laster, Walter R [Oviedo, FL; Gambacorta, Domenico [Oviedo, FL

    2012-02-14

    A pre-mixer assembly associated with a fuel supply system for mixing of air and fuel upstream from a main combustion zone in a gas turbine engine. The pre-mixer assembly includes a swirler assembly disposed about a fuel injector of the fuel supply system and a pre-mixer transition member. The swirler assembly includes a forward end defining an air inlet and an opposed aft end. The pre-mixer transition member has a forward end affixed to the aft end of the swirler assembly and an opposed aft end defining an outlet of the pre-mixer assembly. The aft end of the pre-mixer transition member is spaced from a base plate such that a gap is formed between the aft end of the pre-mixer transition member and the base plate for permitting a flow of purge air therethrough to increase a velocity of the air/fuel mixture exiting the pre-mixer assembly.

  18. Fuel premixing module for gas turbine engine combustor

    NASA Technical Reports Server (NTRS)

    Chin, Jushan (Inventor); Rizk, Nader K. (Inventor); Razdan, Mohan K. (Inventor); Marshall, Andre W. (Inventor)

    2005-01-01

    A fuel-air premixing module is designed to reduce emissions from a gas turbine engine. In one form, the premixing module includes a central pilot premixer module with a main premixer module positioned thereround. Each of the portions of the fuel-air premixing module include an axial inflow swirler with a plurality of fixed swirler vanes. Fuel is injected into the main premixer module between the swirler vanes of the axial inflow swirler and at an acute angle relative to the centerline of the premixing module.

  19. Insulin management of type 2 diabetes mellitus.

    PubMed

    Petznick, Allison

    2011-07-15

    Insulin therapy is recommended for patients with type 2 diabetes mellitus and an initial A1C level greater than 9 percent, or if diabetes is uncontrolled despite optimal oral glycemic therapy. Insulin therapy may be initiated as augmentation, starting at 0.3 unit per kg, or as replacement, starting at 0.6 to 1.0 unit per kg. When using replacement therapy, 50 percent of the total daily insulin dose is given as basal, and 50 percent as bolus, divided up before breakfast, lunch, and dinner. Augmentation therapy can include basal or bolus insulin. Replacement therapy includes basal-bolus insulin and correction or premixed insulin. Glucose control, adverse effects, cost, adherence, and quality of life need to be considered when choosing therapy. Metformin should be continued if possible because it is proven to reduce all-cause mortality and cardiovascular events in overweight patients with diabetes. In a study comparing premixed, bolus, and basal insulin, hypoglycemia was more common with premixed and bolus insulin, and weight gain was more common with bolus insulin. Titration of insulin over time is critical to improving glycemic control and preventing diabetes-related complications.

  20. A premixed hydrogen/oxygen catalytic igniter

    NASA Technical Reports Server (NTRS)

    Green, James M.

    1989-01-01

    The catalytic ignition of hydrogen and oxygen propellants was studied using a premixing hydrogen/oxygen injector. The premixed injector was designed to eliminate problems associated with catalytic ignition caused by poor propellant mixing in the catalyst bed. Mixture ratio, mass flow rate, and propellant inlet temperature were varied parametrically in testing, and a pulse mode life test of the igniter was conducted. The results of the tests showed that the premixed injector eliminated flame flashback in the reactor and increased the life of the igniter significantly. The results of the experimental program and a comparison with data collected in a previous program are given.

  1. Premixed autoignition in compressible turbulence

    NASA Astrophysics Data System (ADS)

    Konduri, Aditya; Kolla, Hemanth; Krisman, Alexander; Chen, Jacqueline

    2016-11-01

    Prediction of chemical ignition delay in an autoignition process is critical in combustion systems like compression ignition engines and gas turbines. Often, ignition delay times measured in simple homogeneous experiments or homogeneous calculations are not representative of actual autoignition processes in complex turbulent flows. This is due the presence of turbulent mixing which results in fluctuations in thermodynamic properties as well as chemical composition. In the present study the effect of fluctuations of thermodynamic variables on the ignition delay is quantified with direct numerical simulations of compressible isotropic turbulence. A premixed syngas-air mixture is used to remove the effects of inhomogeneity in the chemical composition. Preliminary results show a significant spatial variation in the ignition delay time. We analyze the topology of autoignition kernels and identify the influence of extreme events resulting from compressibility and intermittency. The dependence of ignition delay time on Reynolds and turbulent Mach numbers is also quantified. Supported by Basic Energy Sciences, Dept of Energy, United States.

  2. LEM-CF Premixed Tool Kit

    SciTech Connect

    2015-01-19

    The purpose of LEM-CF Premixed Tool Kit is to process premixed flame simulation data from the LEM-CF solver (https://fileshare.craft-tech.com/clusters/view/lem-cf) into a large-eddy simulation (LES) subgrid model database. These databases may be used with a user-defined-function (UDF) that is included in the Tool Kit. The subgrid model UDF may be used with the ANSYS FLUENT flow solver or other commercial flow solvers.

  3. Premixed turbulent flame propagation in microgravity

    NASA Technical Reports Server (NTRS)

    Menon, S.; Jagoda, J.; Sujith, R.

    1995-01-01

    To reduce pollutant formation there is, at present, an increased interest in employing premixed fuel/air mixture in combustion devices. It is well known that greater control over local temperature can be achieved with premixed flames and with lean premixed mixtures, significant reduction of pollutants such as NO(x) can be achieved. However, an issue that is still unresolved is the predictability of the flame propagation speed in turbulent premixed mixtures, especially in lean mixtures. Although substantial progress has been made in recent years, there is still no direct verification that flame speeds in turbulent premixed flows are highly predictable in complex flow fields found in realistic combustors. One of the problems associated with experimental verification is the difficulty in obtaining access to all scales of motion in typical high Reynolds number flows, since, such flows contain scales of motion that range from the size of the device to the smallest Kolmogorov scale. The overall objective of this study is to characterize the behavior of turbulent premixed flames at reasonable high Reynolds number, Re(sub L). Of particular interest here is the thin flame limit where the laminar flame thickness is much smaller than the Kolmogorov scale. Thin flames occur in many practical combustion devices and will be numerically studied using a recently developed new formulation that is briefly described.

  4. Recommendations for improving adherence to type 2 diabetes mellitus therapy--focus on optimizing insulin-based therapy.

    PubMed

    Campbell, R Keith

    2012-04-01

    Despite its unsurpassed efficacy in the management of diabetes, insulin has been resisted and feared for its risk of side effects (ie, weight gain, hypoglycemia). Many patients and providers have perceived insulin as a last resort therapy given to patients with a poor prognosis, and some patients even as a form of punishment for poor self-management. Also, fear of needles is a constant concern. Fortunately, these challenges to insulin use may be overcome via patient education as well as new developments in insulin therapy. Insulin formulations have been developed that possess pharmacokinetic profiles better adapted to the physiologic needs of patients with type 2 diabetes mellitus (T2DM), including rapid- and long-acting insulin analogues, as well as premixed formulations. Appropriate use of these agents is associated with improved glycemic control, higher levels of adherence to treatment, and lower healthcare costs. A variety of pen delivery systems for insulin delivery are available that allow for easier, more discreet, and more accurately dosed insulin therapy. Patients generally prefer pen delivery systems, and they are associated with greater adherence and better glycemic control as compared with vial and syringe use. In addition to the ever-increasing variety of insulin formulations and delivery systems, educational initiatives are absolutely vital in order to overcome the limited knowledge about diabetes, self-management, and coping skills that can be seen in a large proportion of people with T2DM. Improved adherence to treatment, better outcomes, and reduced costs are contingent upon the appropriate use of, and full access to, appropriate treatment and patient education.

  5. Overview of insulin delivery pen devices.

    PubMed

    Kroon, Lisa

    2009-01-01

    To review currently available insulin delivery pen devices for use in diabetes and to describe their primary benefits and drawbacks in comparison with the traditional vial/syringe method of insulin administration. Not applicable. Insulin delivery pen devices are available for most types of insulin, including all insulin analog preparations and insulin premixes with rapid-acting insulin or regular insulin with neutral protamine Hagedorn insulin. Some devices have a replaceable insulin cartridge (categorized as reusable or durable); other devices are prefilled and are disposed of after the insulin reservoir is emptied. Insulin delivery pens offer several advantages over the vial and syringe method of injection, including greater ease and discretion of use and improved portability, adherence, and dosing accuracy. The tactile and auditory feedback provided by the dosing dial on insulin delivery pen devices may be particularly helpful for patients who have impaired manual dexterity or vision. Studies also show a strong preference among patients in favor of insulin delivery pen devices compared with the vial/syringe method. Finally, despite greater per-unit cost, insulin delivery pen devices have also been associated with reductions in health resource use and associated costs compared with vial/syringe therapy. Insulin delivery pen devices offer another option to patients with diabetes for insulin administration. They are associated with not only improved ease of use but also improved dosing accuracy and adherence to therapy. To develop the most suitable insulin regimens for their patients, health providers should be informed about available insulin delivery pen devices.

  6. Analogue Gravity.

    PubMed

    Barceló, Carlos; Liberati, Stefano; Visser, Matt

    2011-01-01

    Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing) and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity).

  7. Turbulent Premixed Flames in Microgravity

    NASA Technical Reports Server (NTRS)

    Menon, Suresh

    1996-01-01

    The experimental cold-flow facility is now full operational and is currently being used to obtain baseline turbulence data in a Couette flow. The baseline turbulence data is necessary to confirm the capability of the chosen device to generate and maintain the required turbulence intensity. Subsequent reacting flow studies will assume that a similar turbulent flow field exists ahead of the premixed flame. Some modifications and refinements had to be made to enable accurate measurements. It consists of two rollers, one (driven by a motor) which drives a continuous belt and four smaller rollers used to set the belt spacing and tension to minimize belt flutter. The entire assemble is enclosed in a structure that has the dimensions to enable future drop tower experiments of the hot facility. All critical dimensions are the same as the original plans except for the pulley ratio which has been changed to enable a wider operating regime in terms of the Reynolds number. With the current setup, Reynolds numbers as low as 100 and as high as 14,000 can be achieved. This is because the in-between belt spacing can be varied from 1 cm to 7.6 cm, and the belt speed can be accurately varied from .15 m/sec to 3.1 m/sec.

  8. Design factors for stable lean premix combustion

    SciTech Connect

    Richards, G.A.; Yip, M.J.; Gemmen, R.S.

    1995-10-01

    The Advanced Turbine Systems (ATS) program includes the development of low-emission combustors. Low emissions have already been achieved by premixing fuel and air to avoid the hot gas pockets produced by nozzles without premixing. While the advantages of premixed combustion have been widely recognized, turbine developers using premixed nozzles have experienced repeated problems with combustion oscillations. Left uncontrolled, these oscillations can lead to pressure fluctuations capable of damaging engine hardware. Elimination of such oscillations is often difficult and time consuming - particularly when oscillations are discovered in the last stages of engine development. To address this issue, METC is studying oscillating combustion from lean premixing fuel nozzles. These tests are providing generic information on the mechanisms that contribute to oscillating behavior in gas turbines. METC is also investigating the use of so-called {open_quotes}active{close_quotes} control of combustion oscillations. This technique periodically injects fuel pulses into the combustor to disrupt the oscillating behavior. Recent results on active combustion control are presented in Gemmen et al. (1995) and Richards et al. (1995). This paper describes the status of METC efforts to avoid oscillations through simple design changes.

  9. Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study.

    PubMed

    Mirzaei, K; Hossein-Nezhad, A; Keshavarz, S A; Eshaghi, S M; Koohdani, F; Saboor-Yaraghi, A A; Hosseini, S; Tootee, A; Djalali, M

    2014-02-01

    Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the cytokine profile and insulin resistance. Moreover, we evaluated the pathways of vitamin D receptor (VDR), PPARγ and PGC1α gene expressions which may lead to insulin resistance following treatment with either alphacalcidol or placebo. A total of 94 obese participants (BMI≥30) were recruited for the current double blind clinical trial study. Patients were divided into two intervention (N.=40) and control groups (N.=54) based on the stratified randomized method. One-Alpha® Capsules 1 microgram: alfacalcidol (1-α hydroxyvitamin D3) and placebo were given to subjects once a day for 8 weeks. Analysis of body composition was performed with use of Body Composition Analyzer. The circulating levels of TNF-α, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, and 25-Hydroxy Vi-tamin D were measured with the use of EIA method. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. The real-time PCR using specific primer pairs for VDR, PGC1α, PPARγ, and β-actin was performed. The FPG, fat percent and PTH levels were decreased and the levels of HDL-cholesterol and 25-hydroxy vitamin D were significantly increased after treatment with Alfacalcidol. Regarding to cytokines levels, the levels of IL6 were significantly decreased and IL10 were significantly increased in Alfacalcidol group in comparison with the control group. The relative expressions of VDR, PGC1α, and PPARγ genes significantly

  10. Soot Formation in Laminar Premixed Flames

    NASA Technical Reports Server (NTRS)

    Xu, F.; Krishnan, S. S.; Faeth, G. M.

    1999-01-01

    Soot processes within hydrocarbon-fueled flames affect emissions of pollutant soot, thermal loads on combustors, hazards of unwanted fires and capabilities for computational combustion. In view of these observations, the present study is considering processes of soot formation in both burner-stabilized and freely-propagating laminar premixed flames. These flames are being studied in order to simplify the interpretation of measurements and to enhance computational tractability compared to the diffusion flame environments of greatest interest for soot processes. In addition, earlier studies of soot formation in laminar premixed flames used approximations of soot optical and structure properties that have not been effective during recent evaluations, as well as questionable estimates of flow residence times). The objective of present work was to exploit methods of avoiding these difficulties developed for laminar diffusion flames to study soot growth in laminar premixed flames. The following description of these studies is brief.

  11. Chaos in an imperfectly premixed model combustor

    SciTech Connect

    Kabiraj, Lipika Saurabh, Aditya; Paschereit, Christian O.; Karimi, Nader; Sailor, Anna; Mastorakos, Epaminondas; Dowling, Ann P.

    2015-02-15

    This article reports nonlinear bifurcations observed in a laboratory scale, turbulent combustor operating under imperfectly premixed mode with global equivalence ratio as the control parameter. The results indicate that the dynamics of thermoacoustic instability correspond to quasi-periodic bifurcation to low-dimensional, deterministic chaos, a route that is common to a variety of dissipative nonlinear systems. The results support the recent identification of bifurcation scenarios in a laminar premixed flame combustor (Kabiraj et al., Chaos: Interdiscip. J. Nonlinear Sci. 22, 023129 (2012)) and extend the observation to a practically relevant combustor configuration.

  12. GAIN Premix Facility: an innovative approach for improving access to quality vitamin and mineral premix in fortification initiatives.

    PubMed

    Guinot, Philippe; Jallier, Vincent; Blasi, Alessandro; Guyondet, Christophe; Van Ameringen, Marc

    2012-12-01

    Vitamin and mineral premix is one of the most significant recurring input costs for large-scale food fortification programs. A number of barriers exist to procuring adequate quality premix, including accessing suppliers, volatile prices for premix, lack of quality assurance and monitoring of delivered products, and lack of funds to purchase premix. To develop and test a model to procure premix through a transparent and efficient process in which an adequate level of quality is guaranteed and a financial mechanism is in place to support countries or specific target groups when there are insufficient resources to cover the cost of premix. Efforts focused on premixes used to fortify flour, such as wheat or maize (iron, zinc, B vitamins, and vitamin A), edible oils (vitamins A and D), and other food vehicles, such as fortified complementary foods, complementary food supplements, and condiments. A premix procurement model was set up with three distinct components: a certification process that establishes industry-wide standards and guidelines for premix, a procurement facility that makes premix more accessible to countries and private industry engaged in fortification, and a credit facility mechanism that helps projects finance premix purchases. After three years of operation, 15 premix suppliers and 29 micronutrient manufacturers have been certified, and more than US$23 million worth of premix that met quality standards has been supplied in 34 countries in Africa, Central and Southern Asia, and Eastern Europe, reaching an estimated 242 million consumers. The Premix Facility demonstrated its effectiveness in ensuring access to high-quality premixes, therefore enabling the success of various fortification programs.

  13. Large-Eddy Simulation of Premixed and Partially Premixed Turbulent Combustion Using a Level Set Method

    NASA Astrophysics Data System (ADS)

    Duchamp de Lageneste, Laurent; Pitsch, Heinz

    2001-11-01

    Level-set methods (G-equation) have been recently used in the context of RANS to model turbulent premixed (Hermann 2000) or partially premixed (Chen 1999) combustion. By directly taking into account unsteady effects, LES can be expected to improve predictions over RANS. Since the reaction zone thickness of premixed flames in technical devices is usually much smaller than the LES grid spacing, chemical reactions completely occur on the sub-grid scales and hence have to be modeled entirely. In the level-set methodology, the flame front is represented by an arbitrary iso-surface G0 of a scalar field G whose evolution is described by the so-called G-equation. This equation is only valid at G=G_0, and hence decoupled from other G levels. Heat release is then modeled using a flamelet approach in which temperature is determined as a function of G and the mixture-fraction Z. In the present study, the proposed approach has been formulated for LES and validated using data from a turbulent Bunsen burner experiment (Chen, Peters 1996). Simulation of an experimental Lean Premixed Prevapourised (LPP) dump combustor (Besson, Bruel 1999, 2000) under different premixed or partially premixed conditions will also be presented.

  14. Premixed flame stabilization on a bluff body

    SciTech Connect

    Hertzberg, J.R.; Talbot, L.

    1986-01-01

    This paper studies the effects of fluid mechanics on combustion, the density and velocity fields of a turbulent premixed flame stabilized on a bluff-body flameholder observed by using Rayleigh scattering for single point measurements of density and laser Doppler velocimetry for velocity data. The stabilization region near the flameholder is the focus of this work. There are several motivations for a study of this nature. First, this configuration, in which a premixed flame is stabilized in the free shear layer of a separated wake behind a bluff body has implications for both mixing layer and basic flame anchoring questions, making this a fundamental problem. Second, since most premixed flames require some form of stabilization for laboratory study, understanding the interaction of the stabilization region and the propagating premixed flame is essential for the interpretation of any resultant data. Third, flame stabilization is of ongoing concern for ramjets, turbojet afterburners and other practical combustion systems. Finally, global models of flame stabilization are based on assumptions, such as the presence of stable recirculating vortices and high turbulence in the recirculation zone, which require verification.

  15. Simulation of lean premixed turbulent combustion

    NASA Astrophysics Data System (ADS)

    Bell, J.; Day, M.; Almgren, A.; Lijewski, M.; Rendleman, C.; Cheng, R.; Shepherd, I.

    2006-09-01

    There is considerable technological interest in developing new fuel-flexible combustion systems that can burn fuels such as hydrogen or syngas. Lean premixed systems have the potential to burn these types of fuels with high efficiency and low NOx emissions due to reduced burnt gas temperatures. Although traditional Scientific approaches based on theory and laboratory experiment have played essential roles in developing our current understanding of premixed combustion, they are unable to meet the challenges of designing fuel-flexible lean premixed combustion devices. Computation, with its ability to deal with complexity and its unlimited access to data, has the potential for addressing these challenges. Realizing this potential requires the ability to perform high fidelity simulations of turbulent lean premixed flames under realistic conditions. In this paper, we examine the specialized mathematical structure of these combustion problems and discuss simulation approaches that exploit this structure. Using these ideas we can dramatically reduce computational cost, making it possible to perform high-fidelity simulations of realistic flames. We illustrate this methodology by considering ultra-lean hydrogen flames and discuss how this type of simulation is changing the way researchers study combustion.

  16. Protamine-containing insulin but not analog insulin and duration of insulin use are risk factors for the production of insulin autoantibodies in insulin-treated patients with diabetes mellitus.

    PubMed

    Nishimura, Hidenao; Iizuka, Katsumi; Takeda, Jun

    2014-01-01

    Insulin autoantibodies can be produced by insulin injections but rarely cause severe side effects such as glucose instability and insulin allergy. We study the characteristics of insulin autoantibody-positive diabetic patients with a medical history of insulin therapy using single and multiple (adjusted for age, sex, type of diabetes) logistic regression analyses. Associations between insulin autoantibodies and age, sex, type of diabetes, HbA1c, and serum creatinine were not significant, but the association between insulin autoantibodies and duration of insulin use was significant. Unadjusted and adjusted odds ratios were 1.08 (1.02-1.14) and 1.07 (1.01-1.14), respectively. Unadjusted and adjusted odds ratios for protamine-containing insulin were 3.08 (1.49-6.34) and 4.27 (1.90-9.58), respectively. The adjusted odds ratios for premixed biphasic insulin and intermediate-acting insulin were 2.21 (1.03-4.73) and 2.35 (1.01-5.49), respectively. Associations between insulin autoantibodies and any insulin analog were not significant. These results suggest that protamine-containing insulin and duration of insulin use are risk factors for the production of insulin autoantibodies. If patients with poorly controlled diabetes have a history of protamine-containing insulin therapy over a long time, the appearance of insulin autoantibodies should be monitored.

  17. Flame propagation under partially-premixed conditions

    NASA Technical Reports Server (NTRS)

    Ruetsch, Gregory R.

    1994-01-01

    This study concentrates on developing a better understanding of triple flames. We relax the assumption of zero heat release, address the issue of stabilization, and, in order to investigate the role that heat release plays in flame propagation in partially premixed combustion, we return to a simple flow field and investigate the behavior of flames in a laminar environment. We solve the compressible Navier-Stokes equations in a two-dimensional domain. At the boundaries, we use an inflow boundary condition on the left and nearly-perfect reflective boundary conditions, required to avoid pressure drift, at the outflow and sides. After the flow and flame are initialized, the mixture fraction is varied at the inlet from its uniform stoichiometric value to a tanh profile varying from zero to one. As the mixture fraction gradient reaches the flame surface only the centerline is exposed to the stoichionetric mixture fraction and locally maintains the planar flame speed and reaction rate. Above this point the mixture is fuel rich, and below fuel lean. As a result, these regions of non-unity equivalence ratio burn less, the reaction rate drops, and the local flame speed is reduced. The excess fuel and oxidizer then combine behind the premixed flame along the stoichiometric surface and burn in a trailing diffusion flame. Thus the 'triple' flame refers to the fuel-rich premixed flame, the fuel-lean premixed flame, and the trailing diffusion flame. Due to heat release, the normal velocity across the flame is increased, whereas the tangential component remains unchanged. Far-field flame speed, local flame speed, and their differences are shown as a function of the local mixing thickness. It was also determined that the lateral position of the flame affects stabilization, and the distribution of the reaction rate along the premixed wings of triple flames affects flame propagation.

  18. Dynamics and structure of turbulent premixed flames

    NASA Technical Reports Server (NTRS)

    Bilger, R. W.; Swaminathan, N.; Ruetsch, G. R.; Smith, N. S. A.

    1995-01-01

    In earlier work (Mantel & Bilger, 1994) the structure of the turbulent premixed flame was investigated using statistics based on conditional averaging with the reaction progress variable as the conditioning variable. The DNS data base of Trouve and Poinsot (1994) was used in this investigation. Attention was focused on the conditional dissipation and conditional axial velocity in the flame with a view to modeling these quantities for use in the conditional moment closure (CMC) approach to analysis of kinetics in premixed flames (Bilger, 1993). Two remarkable findings were made: there was almost no acceleration of the axial velocity in the flame front itself; and the conditional scalar dissipation remained as high, or higher, than that found in laminar premixed flames. The first finding was surprising since in laminar flames all the fluid acceleration occurs through the flame front, and this could be expected also for turbulent premixed flames at the flamelet limit. The finding gave hope of inventing a new approach to the dynamics of turbulent premixed flames through use of rapid distortion theory or an unsteady Bernoulli equation. This could lead to a new second order closure for turbulent premixed flames. The second finding was contrary to our measurements with laser diagnostics in lean hydrocarbon flames where it is found that conditional scalar dissipation drops dramatically below that for laminar flamelets when the turbulence intensity becomes high. Such behavior was not explainable with a one-step kinetic model, even at non-unity Lewis number. It could be due to depletion of H2 from the reaction zone by preferential diffusion. The capacity of the flame to generate radicals is critically dependent on the levels of H2 present (Bilger, et al., 1991). It seemed that a DNS computation with a multistep reduced mechanism would be worthwhile if a way could be found to make this feasible. Truly innovative approaches to complex problems often come only when there is the

  19. The behavior of partially premixed flames

    NASA Astrophysics Data System (ADS)

    Choi, Chun Wai

    In this investigation, we have characterized the structure of two-dimensional partially-premixed slot burner flames through the measurement of the heat release topography, and the temperature and velocity distribution. The measurements were used to infer the flame stretch and the response of the local propagation speed of the inner rich premixed reaction zone in these flames to stretch rate variations due to hydrodynamic and curvature effects. The inner premixed reaction zone of the PPFs exhibits a highly curved portion near its tip and planar topography along its lower portion. An "effective flame speed" was characterized for two flames beyond the rich flammability limit that can only burn in a partially-premixed mode due to the synergy between the inner premixed and outer nonpremixed reaction zones. The reaction zone speed in the curved region increases significantly during the transition from a planar to curved topology due to curvature effects. The Markstein relation must be suitably modified to account for the curvature of the reaction zones for flame with negative curvature. Negative curvature increases the local value of the flame speed above the unstretched flame speed Su o while positive curvature decreases it below that value. Although curvature effects are included in the definition of stretch, they are not fully accounted for by the Su(kappa) Markstein linear relation. This implies that the curvature has an influence on Su through kappa and another more explicit effect. The propagation of triple flames in premixed and nonpremixed jet modes was investigated. The response of flame speed at the triple point to stretch has a turning behavior due to the variation of the radius of curvature while the flame is propagating downward. In normal gravity, the buoyant gases accelerate the flow in a direction opposite to the gravity vector, causing air entrainment, which enhances the mixing of the reactants with ambient laboratory air and consequently, influences the

  20. Assessment of biochemical control of acromegaly during treatment with somatostatin analogues by oral glucose load and insulin-like growth factor I.

    PubMed

    Scacchi, M; Carzaniga, C; Vitale, G; Fatti, L M; Pecori Giraldi, F; Andrioli, M; Cattaneo, A; Cavagnini, F

    2011-10-01

    The use of oral glucose tolerance test (OGTT) in evaluating biochemical control in acromegalic patients on somatostatin analogues (SSA) has recently been questioned. To gain further insights into this topic, we analyzed basal and nadir GH levels during OGTT in acromegalic patients on SSA. Basal IGF-I and GH values, as well as GH levels along the test, were analyzed in 115 standard OGTT performed in 33 acromegalic patients followed up between 1993 and 2009. All patients were on SSA at the time of the study; 22 of them had previously undergone unsuccessful surgery. No patient had undergone radiotherapy. GH suppression was considered normal when the hormonal value fell to <1 μg/l during OGTT. Diagnostic accuracy was analyzed by receiver operating characteristic (ROC) curves. ROC analysis showed that the GH basal value yielding the best specificity (100%) was 3.9 μg/l. All patients with basal GH>3.9 μg/l displayed lack of GH suppression after OGTT and 80% also displayed high IGF-I. Conversely, patients with basal GH<3.9 μg/l presented a variable biochemical pattern with half of them failing to suppress GH after OGTT and 36.6% displaying high IGF-I levels. Our results show that baseline GH levels >3.9 μg/l are predictive of absent OGTT-dependent GH suppression; however, 20% of these patients display partial biochemical control (normal IGF-I levels). On the other hand, basal GH values <3.9 μg/l are not predictive of GH suppressibility by glucose and are often discordant with IGF-I levels.

  1. Studies of Premixed Laminar and Turbulent Flames at Microgravity

    NASA Technical Reports Server (NTRS)

    Kwon, O. C.; Abid, M.; Porres, J.; Liu, J. B.; Ronney, P. D.; Struk, P. M.; Weiland, K. J.

    2003-01-01

    Several topics relating to premixed flame behavior at reduced gravity have been studied. These topics include: (1) flame balls; (2) flame structure and stability at low Lewis number; (3) experimental simulation of buoyancy effects in premixed flames using aqueous autocatalytic reactions; and (4) premixed flame propagation in Hele-Shaw cells. Because of space limitations, only topic (1) is discussed here, emphasizing results from experiments on the recent STS-107 Space Shuttle mission, along with numerical modeling efforts.

  2. Turbulent flame propagation in partially premixed flames

    NASA Technical Reports Server (NTRS)

    Poinsot, T.; Veynante, D.; Trouve, A.; Ruetsch, G.

    1996-01-01

    Turbulent premixed flame propagation is essential in many practical devices. In the past, fundamental and modeling studies of propagating flames have generally focused on turbulent flame propagation in mixtures of homogeneous composition, i.e. a mixture where the fuel-oxidizer mass ratio, or equivalence ratio, is uniform. This situation corresponds to the ideal case of perfect premixing between fuel and oxidizer. In practical situations, however, deviations from this ideal case occur frequently. In stratified reciprocating engines, fuel injection and large-scale flow motions are fine-tuned to create a mean gradient of equivalence ratio in the combustion chamber which provides additional control on combustion performance. In aircraft engines, combustion occurs with fuel and secondary air injected at various locations resulting in a nonuniform equivalence ratio. In both examples, mean values of the equivalence ratio can exhibit strong spatial and temporal variations. These variations in mixture composition are particularly significant in engines that use direct fuel injection into the combustion chamber. In this case, the liquid fuel does not always completely vaporize and mix before combustion occurs, resulting in persistent rich and lean pockets into which the turbulent flame propagates. From a practical point of view, there are several basic and important issues regarding partially premixed combustion that need to be resolved. Two such issues are how reactant composition inhomogeneities affect the laminar and turbulent flame speeds, and how the burnt gas temperature varies as a function of these inhomogeneities. Knowledge of the flame speed is critical in optimizing combustion performance, and the minimization of pollutant emissions relies heavily on the temperature in the burnt gases. Another application of partially premixed combustion is found in the field of active control of turbulent combustion. One possible technique of active control consists of pulsating

  3. [Transdermal delivery of insulin].

    PubMed

    Sevast'ianov, V I; Salomatina, L A; Kuznetsova, E G; Iakovleva, N V; Shumakov, V I

    2003-01-01

    A possibility is studied of the transdermal delivery of insulin by using a mixture of synthetic analogues of phosphoglycerides (SAP), as a potential activator of hormone diffusion, through the skin. Experimentally in vitro, it was proven that the diffusion of insulin through the skin of two types of transdermal therapeutic form (TTF)--matrix-type and matrix-hydrogel-type--is possible only in presence of activator SAP-M-99. The detected optimal composition of insulin matrix TTF with the area of 40 sq cm enabled a trandermal hormone diffusion speed of 0.26 UNITS/h, which is compatible with the secretion of insulin by the pancreas of an adult (0.25-1.5 UNITS/h). A change-over for the matrix-hydrogel system of insulin delivery based on a 40 sq cm collagenous sponge enabled to increase the insulin diffusion up to 0.54 UNITS/h.

  4. Insulin pump therapy in pregnancy.

    PubMed

    Kesavadev, Jothydev

    2016-09-01

    Control of blood glucose during pregnancy is difficult because of wide variations, ongoing hormonal changes and mood swings. The need for multiple injections, pain at the injection site, regular monitoring and skillful handling of the syringes/pen further makes insulin therapy inconvenient. Insulin pump is gaining popularity in pregnancy because it mimics the insulin delivery of a healthy human pancreas. Multiple guidelines have also recommended the use of insulin pump in pregnancy to maintain the glycaemic control. The pump can release small doses of insulin continuously (basal), or a bolus dose close to mealtime to control the spike in blood glucose after a meal and the newer devices can shut down insulin delivery before the occurrence of hypoglycaemia. Pump insulin of choice is rapid acting analogue insulin. This review underscores the role of insulin pump in pregnancy, their usage, advantages and disadvantages in the light of existing literature and clinic experience.

  5. Gravity Effects Observed In Partially Premixed Flames

    NASA Technical Reports Server (NTRS)

    Puri, Ishwar K.; Aggarwal, Suresh K.; Lock, Andrew J.; Gauguly, Ranjan; Hegde, Uday

    2003-01-01

    Partially premixed flames (PPFs) contain a rich premixed fuel air mixture in a pocket or stream, and, for complete combustion to occur, they require the transport of oxidizer from an appropriately oxidizer-rich (or fuel-lean) mixture that is present in another pocket or stream. Partial oxidation reactions occur in fuel-rich portions of the mixture and any remaining unburned fuel and/or intermediate species are consumed in the oxidizer-rich portions. Partial premixing, therefore, represents that condition when the equivalence ratio (phi) in one portion of the flowfield is greater than unity, and in another section its value is less than unity. In general, for combustion to occur efficiently, the global equivalence ratio is in the range fuel-lean to stoichiometric. These flames can be established by design by placing a fuel-rich mixture in contact with a fuel-lean mixture, but they also occur otherwise in many practical systems, which include nonpremixed lifted flames, turbulent nonpremixed combustion, spray flames, and unwanted fires. Other practical applications of PPFs are reported elsewhere. Although extensive experimental studies have been conducted on premixed and nonpremixed flames under microgravity, there is a absence of previous experimental work on burner stabilized PPFs in this regard. Previous numerical studies by our group employing a detailed numerical model showed gravity effects to be significant on the PPF structure. We report on the results of microgravity experiments conducted on two-dimensional (established on a Wolfhard-Parker slot burner) and axisymmetric flames (on a coannular burner) that were investigated in a self-contained multipurpose rig. Thermocouple and radiometer data were also used to characterize the thermal transport in the flame.

  6. Displacement speeds in turbulent premixed flame simulations

    SciTech Connect

    Day, Marcus S.; Shepherd, Ian G.; Bell, J.; Grcar, Joseph F.; Lijewski, Michael J.

    2007-07-01

    The theory of turbulent premixed flames is based on acharacterization of the flame as a discontinuous surface propagatingthrough the fluid. The displacement speed, defined as the local speed ofthe flame front normal to itself, relative to the unburned fluid,provides one characterization of the burning velocity. In this paper, weintroduce a geometric approach to computing displacement speed anddiscuss the efficacy of the displacement speed for characterizing aturbulent flame.

  7. Premixed Turbulent Flame Propagation in Microgravity

    NASA Technical Reports Server (NTRS)

    Menon, Suresh

    1999-01-01

    A combined numerical-experimental study has been carried out to investigate the structure and propagation characteristics of turbulent premixed flames with and without the influence of buoyancy. Experimentally, the premixed flame characteristics are studied in the wrinkled regime using a Couette flow facility and an isotropic flow facility in order to resolve the scale of flame wrinkling. Both facilities were chosen for their ability to achieve sustained turbulence at low Reynolds number. This implies that conventional diagnostics can be employed to resolve the smallest scales of wrinkling. The Couette facility was also built keeping in mind the constraints imposed by the drop tower requirements. Results showed that the flow in this Couette flow facility achieves full-developed turbulence at low Re and all turbulence statistics are in good agreement with past measurements on large-scale facilities. Premixed flame propagation studies were then carried out both using the isotropic box and the Couette facility. Flame imaging showed that fine scales of wrinkling occurs during flame propagation. Both cases in Ig showed significant buoyancy effect. To demonstrate that micro-g can remove this buoyancy effect, a small drop tower was built and drop experiments were conducted using the isotropic box. Results using the Couette facility confirmed the ability to carry out these unique reacting flow experiments at least in 1g. Drop experiments at NASA GRC were planned but were not completed due to termination of this project.

  8. Simulation of lean premixed turbulent combustion

    SciTech Connect

    Bell, John B.; Day, Marcus S.; Almgren, Ann S.; Lijewski, MichaelJ.; Rendleman, Charles A.; Cheng, Robert K.; Shepherd, Ian G.

    2006-06-25

    There is considerable technological interest in developingnew fuel-flexible combustion systems that can burn fuels such ashydrogenor syngas. Lean premixed systems have the potential to burn thesetypes of fuels with high efficiency and low NOx emissions due to reducedburnt gas temperatures. Although traditional scientific approaches basedon theory and laboratory experiment have played essential roles indeveloping our current understanding of premixed combustion, they areunable to meet the challenges of designing fuel-flexible lean premixedcombustion devices. Computation, with itsability to deal with complexityand its unlimited access to data, hasthe potential for addressing thesechallenges. Realizing this potential requires the ability to perform highfidelity simulations of turbulent lean premixed flames under realisticconditions. In this paper, we examine the specialized mathematicalstructure of these combustion problems and discuss simulation approachesthat exploit this structure. Using these ideas we can dramatically reducecomputational cost, making it possible to perform high-fidelitysimulations of realistic flames. We illustrate this methodology byconsidering ultra-lean hydrogen flames and discuss how this type ofsimulation is changing the way researchers study combustion.

  9. Numerical simulation of premixed turbulent methane combustion

    SciTech Connect

    Day, Marc S.; Bell, John B.; Almgren, Ann S.; Beckner, Vincent E.; Lijewski, Michael J.; Cheng, Robert; Shepherd, Ian; Johnson, Matthew

    2003-06-14

    With adaptive-grid computational methodologies and judicious use of compressible and low Mach number combustion models, we are carrying out three-dimensional, time-dependent direct numerical simulations of a laboratory-scale turbulent premixed methane burner. In the laboratory experiment, turbulence is generated by a grid located in the throat of a 50mm diameter circular nozzle; swirl is be introduced by four tangential air jets spaced uniformly around the circumference of the nozzle just above the turbulence grid. A premixed methane flame is stabilized above the nozzle in the central core region where a velocity deficit is induced7the swirling flow. The time-dependent flow field inside the nozzle, from the turbulence grid and the high-speed jets, to the nozzle exit plane is simulated using an adaptive-grid embedded-boundary compressible Navier-Stokes solver. The compressible calculation then provides time-dependent boundary conditions for an adaptive low Mach number model of the swirl-stabilized premixed flame. The low Mach model incorporates detailed chemical kinetics and species transport using 20 species and 84 reactions. Laboratory diagnostics available for comparisons include characterizations of the flow field just down stream of the nozzle exit plane, and flame surface statistics, such as mean location, wrinkling and crossing frequencies.

  10. Premixed calcium silicate cement for endodontic applications

    PubMed Central

    Persson, Cecilia; Engqvist, Håkan

    2011-01-01

    Calcium silicate-based materials (also called MTA) are increasingly being used in endodontic applications. However, the handling properties of MTA are not optimal when it comes to injectability and cohesion. Premixing the cements using glycerol avoids these issues. However, there is a lack of data on the effect of common cement variables on important properties of premixed cements for endodontic applications. In this study, the effects of liquid-to-powder ratio, amount of radiopacifier and amount of calcium sulfate (added to control the setting time) were screened using a statistical model. In the second part of the study, the liquid-to-powder ratio was optimized for cements containing three different amounts of radiopacifier. Finally, the effect of using glycerol rather than water was evaluated in terms of radiopacity. The setting time was found to increase with the amount of radiopacifier when the liquid-to-powder ratio was fixed. This was likely due to the higher density of the radiopacifier in comparison to the calcium silicate, which gave a higher liquid-to-powder ratio in terms of volume. Using glycerol rather than water to mix the cements led to a decrease in radiopacity of the cement. In conclusion, we were able to produce premixed calcium silicate cements with acceptable properties for use in endodontic applications. PMID:23507729

  11. Efficacy and safety of biphasic insulin aspart and biphasic insulin lispro mix in patients with type 2 diabetes: A review of the literature

    PubMed Central

    Kumar, Ajay

    2016-01-01

    Type 2 diabetes (T2D) represents an escalating burden worldwide, particularly in China and India. Compared with Caucasians, Asian people with diabetes have lower body mass index, increased visceral adiposity, and postprandial glucose (PPG)/insulin resistance. Since postprandial hyperglycemia contributes significantly to total glycemic burden and is associated with heightened cardiovascular risk, targeting PPG early in T2D is paramount. Premixed insulin regimens are widely used in Asia due to their convenience and effectiveness. Data from randomized controlled trials and observational studies comparing efficacy and safety of biphasic insulin aspart 30 (BIAsp 30) with biphasic insulin lispro mix (LM 25/50) and versus other insulin therapies or oral antidiabetic drugs (OADs) in T2D demonstrated that BIAsp 30 and LM 25/50 were associated with similar or greater improvements in glycemic control versus comparator regimens, such as basal–bolus insulin, in insulin-naÏve, and prior insulin users. Studies directly comparing BIAsp 30 and LM 25 provided conflicting glycemic control results. Safety data generally showed increased hypoglycemia and weight gain with premixed insulins versus basal–bolus insulin or OADs. However, large observational trials documented improvements in glycated hemoglobin, PPG, and hypoglycemia with BIAsp 30 in multi-ethnic patient populations. In summary, this literature review demonstrates that premixed insulin regimens are an appropriate and effective treatment choice in T2D. PMID:27186543

  12. Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

    SciTech Connect

    Salem, M.A.M.; Phares, C.K.

    1986-03-01

    The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate (U-/sup 14/C)glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10/sup 5/ cells/ml) were incubated with either (/sup 125/I)insulin or (/sup 125/I)hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and /sup 14/C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro.

  13. A Comparison of the Effects of the GLP-1 Analogue Liraglutide and Insulin Glargine on Endothelial Function and Metabolic Parameters: A Randomized, Controlled Trial Sapporo Athero-Incretin Study 2 (SAIS2)

    PubMed Central

    Nomoto, Hiroshi; Miyoshi, Hideaki; Furumoto, Tomoo; Oba, Koji; Tsutsui, Hiroyuki; Miyoshi, Arina; Kondo, Takuma; Tsuchida, Kenichi; Atsumi, Tatsuya; Manda, Naoki; Kurihara, Yoshio; Aoki, Shin

    2015-01-01

    Objectives GLP-1 improves hyperglycemia, and it has been reported to have favorable effects on atherosclerosis. However, it has not been fully elucidated whether GLP-1 is able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of the GLP-1 analogue, liraglutide on endothelial function and glycemic metabolism compared with insulin glargine therapy. Materials and Methods In this multicenter, prospective randomized parallel-group comparison study, 31 diabetic outpatients (aged 60.3 ± 10.3 years with HbA1c levels of 8.6 ± 0.8%) with current metformin and/or sulfonylurea treatment were enrolled and randomly assigned to receive liraglutide or glargine therapy once daily for 14 weeks. Flow mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force Monitor), and serum metabolic markers were assessed before and after the treatment period. Results A greater reduction (worsening) in %FMD was observed in the glargine group, although this change was not statistically different from the liraglutide group (liraglutide; 5.7 to 5.4%, glargine 6.7 to 5.7%). The augmentation index, C-peptide index, derivatives of reactive oxygen metabolites and BMI were significantly improved in the liraglutide group. Central systolic blood pressure and NT-proBNP also tended to be improved in the liraglutide-treated group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different. Conclusions Regardless of glycemic improvement, early liraglutide therapy did not affect endothelial function but may provide favorable effects on beta-cell function and cardioprotection in type 2 diabetics without advanced atherosclerosis. Trial Registration UMIN Clinical Trials Registry System as trial ID UMIN000005331. PMID:26284918

  14. Identification of Host Insulin Binding Sites on Schistosoma japonicum Insulin Receptors.

    PubMed

    Stephenson, Rachel J; Toth, Istvan; Liang, Jiening; Mangat, Amanjot; McManus, Donald P; You, Hong

    2016-01-01

    Schistosoma japonicum insulin receptors (SjIRs) have been identified as encouraging vaccine candidates. Interrupting or blocking the binding between host insulin and the schistosome insulin receptors (IRs) may result in reduced glucose uptake leading to starvation and stunting of worms with a reduction in egg output. To further understand how schistosomes are able to exploit host insulin for development and growth, and whether these parasites and their mammalian hosts compete for the same insulin source, we identified insulin binding sites on the SjIRs. Based on sequence analysis and the predicted antigenic structure of the primary sequences of the SjIRs, we designed nine and eleven peptide analogues from SjIR-1 and SjIR-2, respectively. Using the Octet RED system, we identified analogues derived from SjIR-1 (10) and SjIR-2 (20, 21 and 22) with insulin-binding sequences specific for S. japonicum. Nevertheless, the human insulin receptor (HIR) may compete with the SjIRs in binding human insulin in other positions which are important for HIR binding to insulin. However, no binding occurred between insulin and parasite analogues derived from SjIR-1 (2, 7 and 8) and SjIR-2 (14, 16 and 18) at the same locations as HIR sequences which have been shown to have strong insulin binding affinities. Importantly, we found two analogues (1 and 3), derived from SjIR-1, and two analogues (13 and 15) derived from SjIR-2, were responsible for the major insulin binding affinity in S. japonicum. These peptide analogues were shown to have more than 10 times (in KD value) stronger binding capacity for human insulin compared with peptides derived from the HIR in the same sequence positions. Paradoxically, analogues 1, 3, 13 and 15 do not appear to contain major antigenic determinants which resulted in poor antibody responses to native S. japonicum protein. This argues against their future development as peptide-vaccine candidates.

  15. Premixed Combustion Model for Boron Clouds

    NASA Astrophysics Data System (ADS)

    Wang, Mengze; Han, Wang; Chen, Zheng

    2015-11-01

    Boron particle is an ideal additive in solid propellants and fuels due to its very high volumetric heat release. In this study, a premixed combustion model for boron clouds is developed based on a previous combustion model for single boron particle. The flame structure is assumed to be composed of three zones: the preheat zone, the ignition zone, and the reaction zone, and analytical solutions are derived from the governing equations. Consequently the influence of the boron clouds' physical properties on the flame propagation process is investigated.

  16. Effect of premixing on nitric oxide formation

    NASA Technical Reports Server (NTRS)

    Anderson, D. N.

    1973-01-01

    Emissions from a simple 10-cm (4-in.) diameter tube combustor burning a premixed, gaseous propane/air mixture were measured. Inlet conditions included a temperature of 590 K (600 F), pressure of 5.5 atm, and reference velocity of 23 m/s (75 ft/s) for a range of equivalence ratios from the lean limit to slightly richer than stoichiometric. A nitric oxide emission index of 1 g NO2/kg fuel was measured for an equivalence ratio of 0.57.

  17. PDF Modeling of Turbulent Lean Premixed Combustion

    SciTech Connect

    Yilmaz, S.L.; •Givi, P.; Strakey, P.A.

    2007-10-01

    The joint velocity-scalar-frequency probability density function (PDF) methodology is employed for prediction of a bluff-body stabilized lean premixed methane-air flame. A reduced mechanism with CO and NO chemistry is used to describe fuel oxidation. The predicted mean and rms values of the velocity, temperature and concentrations of major and minor species are compared with laboratory measurements. This technical effort was performed in support of the National Energy Technology Laboratory’s on-going research in “Assessment of Turbo-Chemistry Models for Gas Turbine Combustion Emissions” under the RDS contract DE-AC26-04NT41817.

  18. Pragmatic use of insulin degludec/insulin aspart co-formulation: A multinational consensus statement

    PubMed Central

    Kalra, Sanjay; Latif, Zafar A.; Comlekci, Abdurrahman; Galvez, Guillermo Gonzalez; Malik, Rached; Pathan, Md Faruque; Kumar, Ajay

    2016-01-01

    Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of ultra-long-acting basal insulin degludec, with rapid-acting insulin aspart. IDegAsp provides effective, safe, well-tolerated glycemic control, with a low risk of hypoglycemia while allowing flexibility in meal patterns and timing of administration. This consensus statement describes a pragmatic framework to identify patients who may benefit from IDegAsp therapy. It highlights the utility of IDegAsp in type 2 diabetic patients who are insulin-naive, suboptimally controlled on basal or premixed insulin, or dissatisfied with basal–bolus regimens. It also describes potential IDegAsp usage in type 1 diabetic patients. PMID:27366723

  19. Pragmatic use of insulin degludec/insulin aspart co-formulation: A multinational consensus statement.

    PubMed

    Kalra, Sanjay; Latif, Zafar A; Comlekci, Abdurrahman; Galvez, Guillermo Gonzalez; Malik, Rached; Pathan, Md Faruque; Kumar, Ajay

    2016-01-01

    Insulin degludec/insulin aspart (IDegAsp) is a modern coformulation of ultra-long-acting basal insulin degludec, with rapid-acting insulin aspart. IDegAsp provides effective, safe, well-tolerated glycemic control, with a low risk of hypoglycemia while allowing flexibility in meal patterns and timing of administration. This consensus statement describes a pragmatic framework to identify patients who may benefit from IDegAsp therapy. It highlights the utility of IDegAsp in type 2 diabetic patients who are insulin-naive, suboptimally controlled on basal or premixed insulin, or dissatisfied with basal-bolus regimens. It also describes potential IDegAsp usage in type 1 diabetic patients.

  20. Network structure of turbulent premixed flames

    NASA Astrophysics Data System (ADS)

    Singh, Jasmeet; Belur Vishwanath, Rahul; Chaudhuri, Swetaprovo; Sujith, R. I.

    2017-04-01

    In this paper, a generalized description of the complex topology of turbulent premixed flames stabilized in a model gas turbine combustor is obtained using network analysis. Networks are created using the visibility algorithm applied to points on the flame edge obtained from Hydroxyl radical (OH)—Planar Laser Induced Fluorescence images of turbulent premixed flames. The network structure thus obtained showed the emergence of a few massively connected nodes which were found to represent the folded regions of the flame front. These nodes, which are called the hubs of the network, are vital for determining the overall structure of the flame front. Degree distribution of the formulated networks is used to characterize the flame-turbulence interaction inherent in the system. Turbulent flame front networks were found to be rigid enough to be unaffected by random perturbations but highly vulnerable towards coordinated removal of hubs or folds. These findings could serve as the first network-analytic approach to characterize turbulence-flame interaction dynamics with the use of a flourishing network theory, which enhances ongoing works based on vortex dynamics, hydrodynamic stability, and thermo-acoustic instability.

  1. Network structure of turbulent premixed flames.

    PubMed

    Singh, Jasmeet; Belur Vishwanath, Rahul; Chaudhuri, Swetaprovo; Sujith, R I

    2017-04-01

    In this paper, a generalized description of the complex topology of turbulent premixed flames stabilized in a model gas turbine combustor is obtained using network analysis. Networks are created using the visibility algorithm applied to points on the flame edge obtained from Hydroxyl radical (OH)-Planar Laser Induced Fluorescence images of turbulent premixed flames. The network structure thus obtained showed the emergence of a few massively connected nodes which were found to represent the folded regions of the flame front. These nodes, which are called the hubs of the network, are vital for determining the overall structure of the flame front. Degree distribution of the formulated networks is used to characterize the flame-turbulence interaction inherent in the system. Turbulent flame front networks were found to be rigid enough to be unaffected by random perturbations but highly vulnerable towards coordinated removal of hubs or folds. These findings could serve as the first network-analytic approach to characterize turbulence-flame interaction dynamics with the use of a flourishing network theory, which enhances ongoing works based on vortex dynamics, hydrodynamic stability, and thermo-acoustic instability.

  2. Confined superadiabatic premixed flame-flow interaction

    SciTech Connect

    Najm, H.N.

    1995-12-31

    Laminar premixed unity-Lewis number flames are studied numerically, to examine flow-flame interaction in a two-dimensional closed domain. Two opposed planar flame fronts are perturbed sinusoidally and allowed to develop by consuming premixed reactants. Combustion heat release leads to global pressure and temperature rise in the domain, due to confinement. A superadiabatic condition, with products temperature rising with distance behind the flame front, is observed due to stagnation pressure rise. Variations in tangential strain rate behind the perturbed flame fronts, due to flame curvature and heat release, result in a modified local superadiabatic temperature gradient in the products. These variations in temperature gradients are shown to determine the net local confinement-heating rate in the products, leading to corresponding deviations in products temperature, and the local reaction rate along the flame front. These observations, which are not consistent with one-dimensional superadiabatic stagnation flame behavior, are a direct result of the unrestrained unsteady nature of two-dimensional flame-flow interaction.

  3. Internal structure of a premixed turbulent flame

    SciTech Connect

    Rajan, S.; Smith, J.R.; Rambach, G.D.

    1982-10-01

    A pulsed laser and a multielement detector have been used to make instantaneous Rayleigh profiles along a line through a turbulent flame front thus eliminating the effects of flame front motion. The flame front in a premixed turbulent flame moves randomly about a mean position, giving rise to the visually observed flame brush or time-averaged flame thickness which is larger than the instantaneous thickness of the reaction zone. The physical characteristics and statistical properties of such turbulent flames reported previously were deduced from the time histories of Rayleigh scattered laser light at one or two points within the reaction zone. The study was conducted on a premixed propane-air flame stabilized on a rod at the exit plane of a square burner. Turbulence-producing screens below the burner exit controlled turbulent length scales while intensity was controlled with inlet mixture velocity. Turbulence properties of the cold reactants were determined by hot-wire anemometry. Mean and fluctuating velocity in the unburnt and burnt gases were measured using laser Doppler velocimetry. At the low level of turbulence studied, the instantaneous flame front thickness was found to be only slightly greater than the laminar flame thickness, and the magnitude of the density fluctuations only slightly greater than the cold flow turbulence intensity. Mean and rms values of density and velocity; density and velocity probability density functions; spatial density correlations; and comparison of data with the Bray-Moss-Libby model are presented.

  4. Preparation of feed premix for veterinary purposes.

    PubMed

    Franc, Aleš; Lehocký, Róbert; Muselík, Jan; Vetchý, David; Dobšíková, Radka; Modrá, Helena

    2014-10-01

    This experimental study describes the preparation of a veterinary medicated premix containing tetracycline hydrochloride for oral administration to aquatic animals. For the manufacture of the premix, commercially produced animal feed is used, which is intended for consumption in the form of pellets that were coated with a mixture of chlortetracycline hydrochloride and other excipients. Feed pellets were combined with a mixture of an active substance and excipients with a large specific surface (colloidal silica - Aerosil® 200) allowing an easy adhesion to the surface of the pellets, and a solid polymer with a low glass transition point (Eudragit® E) which ensures the formation of a hard coat. A mixture of these substances has been applied to the surface of the pellets either A) in the solid state simply by dry adhesion; B) by coating the pellets with the mixture and additional impregnation with ethanol; or C) the polymer was subsequently applied in solution. In the final stage, the pellets were heated in order to achieve the glass transition point of the polymer to create a solid and mechanically resistant coating. Coated pellets prepared by three methods described above are almost identical in their physical properties. With this technology it is possible to produce a feed mixture with a very low content of the active substance in situ without the need for a complex technological equipment.

  5. A model for premixed combustion oscillations

    SciTech Connect

    Janus, M.C.; Richards, G.A.

    1996-03-01

    Combustion oscillations are receiving renewed research interest due to increasing application of lean premix (LPM) combustion to gas turbines. A simple, nonlinear model for premixed combustion is described; it was developed to explain experimental results and to provide guidance for developing active control schemes based on nonlinear concepts. The model can be used to quickly examine instability trends associated with changes in equivalence ratio, mass flow rate, geometry, ambient conditions, etc. The model represents the relevant processes occurring in a fuel nozzle and combustor analogous to current LPM turbine combustors. Conservation equations for the nozzle and combustor are developed from simple control volume analysis, providing ordinary differential equations that can be solved on a PC. Combustion is modeled as a stirred reactor, with bimolecular reaction between fuel and air. Although focus is on the model, it and experimental results are compared to understand effects of inlet air temperature and open loop control schemes. The model shows that both are related to changes in transport time.

  6. Multiscale Interactions and Backscatter in Premixed Combustion

    NASA Astrophysics Data System (ADS)

    Hamlington, Peter; Towery, Colin; O'Brien, Jeffrey; Poludnenko, Alexei; Urzay, Javier; Ihme, Matthias

    2015-11-01

    Multiscale interactions and energy transfer between turbulence and flames are fundamental to understanding and modeling premixed turbulent reacting flows. To investigate such flows, direct numerical simulations of statistically planar turbulent premixed flames have been performed, and the dynamics of kinetic energy transfer are examined in both spectral and physical spaces. In the spectral analysis, two-dimensional kinetic energy spectra and triadic interactions are computed through the flame brush. It is found that there is suppression of turbulent small-scale motions in the combustion products, along with backscatter of energy for a range of scales near the thermal laminar flame width. In the physical-space analysis, a differential filter is applied to examine the transfer of kinetic energy between subgrid and resolved scales in the context of large eddy simulations. Subgrid-scale backscatter of kinetic energy driven by combustion is found to prevail over forward scatter throughout the flame brush. The spectral- and physical-space analyses thus both suggest an enhancement of reverse-cascade phenomena in the flame brush, which is possibly driven by accumulation of kinetic energy in the scales where combustion-induced heat release is preferentially deployed.

  7. Mutations at the dimer, hexamer, and receptor-binding surfaces of insulin independently affect insulin-insulin and insulin-receptor interactions

    SciTech Connect

    Shoelson, S.E.; Zixian Lu; Parlautan, L.; Lynch, C.S.; Weiss, M.A. )

    1992-02-18

    Mutagenesis of the dimer- and hexamer-forming surfaces of insulin yields analogues with reduced tendencies to aggregate and dramatically altered pharmacokinetic properties. The authors recently showed that one such analogue, HisB1- {yields} Asp, ProB28 {yields} Lys, LysB29 {yields} Pro human insulin (DKP-insulin), has enhanced affinity for the insulin receptor and is useful for studying the structure of the insulin monomer under physiologic solvent conditions. DKP-insulin retains native secondary and tertiary structure in solution and may therefore provide an appropriate baseline for further studies of related analogues containing additional substitutions within the receptor-binding surface of insulin. To test this, they prepared a family of DKP analogues having potency-altering substitutions at the B24 and B25 positions using a streamlined approach to enzymatic semisynthesis which negates the need for amino-group protection. For comparison, similar analogues of native human insulin were prepared by standard semisynthetic methods. The DKP analogues show a reduced tendency to self-associate, as indicated by {sup 1}H-NMR resonance line widths. Such 'template independence' reflects an absence of functional interactions between the B24 and B25 sites and additional substitutions in DKP-insulin and demonstrates that mutations in discrete surfaces of insulin have independent effects on protein structure and function. In particular, the respective receptor-recognition (PheB24, PheB25), hexamer-forming (HisB10), and dimer-forming (ProB28, LysB29) surfaces of insulin may be regarding as independent targets for protein design. DKP-insulin provides an appropriate biophysical model for defining structure-function relationships in a monomeric template.

  8. Insulin and Insulin Resistance

    PubMed Central

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  9. Epinephrine analogues.

    PubMed

    Sneader, W

    2001-11-01

    Tyramine was the first epinephrine analogue to be introduced into medicine, in the early 1900s. It was followed by ephedrine and pseudoephedrine in the 1920s and by the amfetamines a decade later. The popularity of the amfetamines grew throughout the 1930s and 1940s; after that, there was a slowly dawning realization that they were being widely abused. Isoprenaline, introduced in the 1950s, was soon recognized as superior to epinephrine when used as an inhaler by asthmatics, and it remained the drug of choice for the relief of bronchospasm until around 1970. Orciprenaline, which featured an orcinol system, had a long duration of action and was active by mouth; Boehringer marketed it both as an inhaler and as a syrup for the prophylaxis of bronchospasm. The greatly superior bronchodilators salbutamol and terbutaline, launched in 1968 and 1970, respectively, incorporate further variation on the molecular theme that had led to the development of orciprenaline. (c) 2001 Prous Science. All rights reserved.

  10. [Novolet--a pen-device for insulin self-injection by disabled diabetics].

    PubMed

    Kisch, E S; Cohen, Y; Arbeli, S

    1996-05-01

    The prefilled, disposable, insulin pen, Novolet is suitable for disabled diabetics, who cannot use the usual injection syringes or insulin pens without help. Of 16 disabled patients in our care, 10 learned to dial the correct number of units of premixed rapid and intermediate insulins, and to inject themselves with this device. Economic aspects aside, we stress the self-esteem and independence regained by these patients.

  11. Insulin therapy in children and adolescents.

    PubMed

    Tamborlane, William V; Sikes, Kristin A

    2012-03-01

    Insulin therapy is the mainstay of treatment in children and adolescents with type 1 diabetes (T1D) and is a key component in the treatment of type 2 diabetes (T2D) in this population as well. A major aim of current insulin replacement therapy is to simulate the normal pattern of insulin secretion as closely as possible. This aim can best be achieved with basal-bolus therapy using multiple daily injections (MDI) or continuous insulin infusion (CSII) pump therapy. Only a few years ago, options for insulin formulations were limited. There are now more than 10 varieties of biosynthetic human and analogue insulin.

  12. Nongradient diffusion in premixed turbulent flames

    NASA Technical Reports Server (NTRS)

    Libby, Paul A.

    1988-01-01

    Recent theoretical and experimental results demonstrating the interaction between force fields and density inhomogeneities as they arise in premixed turbulent flames are discussed. In such flames, the density fluctuates between two levels, the high density in reactants rho sub r and the low density in products rho sub p, with the ratio rho sub r/rho sub p on the order of five to ten in flows of applied interest. The force fields in such flames arise from the mean pressure drop across the flame or from the Reynolds shear stresses in tangential flames with constrained streamlines. The consequence of the interaction is nongradient turbulent transport, countergradient in the direction normal to the flame and nongradient in the tangential direction. The theoretical basis for these results, the presently available experimental support therefore and the implications for other variable density turbulent flows are discussed.

  13. The structure of particle cloud premixed flames

    NASA Technical Reports Server (NTRS)

    Seshadri, K.

    1993-01-01

    The aim of this study is to provide a numerical and asymptotic description of the structure of planar laminar flames, propagating in a medium containing a uniform cloud of fuel-particles premixed with air. Attention is restricted here to systems where the fuel-particles first vaporize to form a known gaseous fuel, which is then oxidized in the gas-phase. This program is supported for the period September 14, 1991 to September 13, 1992. Some results of the study is shown in Ref. 1. The work summarized in Ref. 1 was initiated prior to September 14, 1991 and was completed on February 1992. Research performed in addition to that described in Ref. 1 in collaboration with Professor A. Linan, is summarized here.

  14. The premixed flame in uniform straining flow

    NASA Technical Reports Server (NTRS)

    Durbin, P. A.

    1982-01-01

    Characteristics of the premixed flame in uniform straining flow are investigated by the technique of activation-energy asymptotics. An inverse method is used, which avoids some of the restrictions of previous analyses. It is shown that this method recovers known results for adiabatic flames. New results for flames with heat loss are obtained, and it is shown that, in the presence of finite heat loss, straining can extinguish flames. A stability analysis shows that straining can suppress the cellular instability of flames with Lewis number less than unity. Strain can produce instability of flames with Lewis number greater than unity. A comparison shows quite good agreement between theoretical deductions and experimental observations of Ishizuka, Miyasaka & Law (1981).

  15. Premixed flames in closed cylindrical tubes

    NASA Astrophysics Data System (ADS)

    Metzener, Philippe; Matalon, Moshe

    2001-09-01

    We consider the propagation of a premixed flame, as a two-dimensional sheet separating unburned gas from burned products, in a closed cylindrical tube. A nonlinear evolution equation, that describes the motion of the flame front as a function of its mean position, is derived. The equation contains a destabilizing term that results from the gas motion induced by thermal expansion and has a memory term associated with vorticity generation. Numerical solutions of this equation indicate that, when diffusion is stabilizing, the flame evolves into a non-planar form whose shape, and its associated symmetry properties, are determined by the Markstein parameter, and by the initial data. In particular, we observe the development of convex axisymmetric or non-axisymmetric flames, tulip flames and cellular flames.

  16. Implementation of Premixed Equilibrium Chemistry Capability in OVERFLOW

    NASA Technical Reports Server (NTRS)

    Olsen, M. E.; Liu, Y.; Vinokur, M.; Olsen, T.

    2003-01-01

    An implementation of premixed equilibrium chemistry has been completed for the OVERFLOW code, a chimera capable, complex geometry flow code widely used to predict transonic flowfields. The implementation builds on the computational efficiency and geometric generality of the solver.

  17. Implementation of Premixed Equilibrium Chemistry Capability in OVERFLOW

    NASA Technical Reports Server (NTRS)

    Olsen, Mike E.; Liu, Yen; Vinokur, M.; Olsen, Tom

    2004-01-01

    An implementation of premixed equilibrium chemistry has been completed for the OVERFLOW code, a chimera capable, complex geometry flow code widely used to predict transonic flowfields. The implementation builds on the computational efficiency and geometric generality of the solver.

  18. Mechanisms of combustion limits in premixed gas flames at microgravity

    NASA Technical Reports Server (NTRS)

    Ronney, Paul D.

    1991-01-01

    A three-year experimental and theoretical research program on the mechanisms of combustion limits of premixed gasflames at microgravity was conducted. Progress during this program is identified and avenues for future studies are discussed.

  19. Studies of premixed laminar and turbulent flames at microgravity

    NASA Technical Reports Server (NTRS)

    Ronney, Paul D.

    1993-01-01

    A two and one-half year experimental and theoretical research program on the properties of laminar and turbulent premixed gas flames at microgravity was conducted. Progress during this program is identified and avenues for future studies are discussed.

  20. Ignition transition in turbulent premixed combustion

    SciTech Connect

    Shy, S.S.; Liu, C.C.; Shih, W.T.

    2010-02-15

    Recently, Shy and his co-workers reported a turbulent ignition transition based on measurements of minimum ignition energies (MIE) of lean premixed turbulent methane combustion in a centrally-ignited, fan-stirred cruciform burner capable of generating intense isotropic turbulence. Using the same methodology, this paper presents new complete MIE data sets for stoichiometric and rich cases at three different equivalence ratios {phi} = 1.0, 1.2 and 1.3, each covering a wide range of a turbulent Karlovitz number (Ka) indicating a time ratio between chemical reaction and turbulence. Thus, ignition transition in premixed turbulent combustion depending on both Ka and {phi} can be identified for the first time. It is found that there are two distinct modes on ignition in randomly stirred methane-air mixtures (ignition transition) separated by a critical Ka where values of Ka{sub c} {approx} 8-26 depending on {phi} with the minimum Ka{sub c} occurring near {phi} = 1. For Ka < Ka{sub c}, MIE increases gradually with Ka, flame kernel formation is similar to laminar ignition remaining a torus, and 2D laser tomography images of subsequent outwardly-propagating turbulent flames show sharp fronts. For Ka > Ka{sub c}, MIE increases abruptly with Ka, flame kernel is disrupted, and subsequent randomly-propagating turbulent flames reveal distributed-like fronts. Moreover, we introduce a reaction zone Peclet number (P{sub RZ}) indicating the diffusivity ratio between turbulence and chemical reaction, such that the aforementioned very scattering MIE data depending on Ka and {phi} can be collapsed into a single curve having two drastically different increasing slopes with P{sub RZ} which are separated by a critical P{sub RZ} {approx} 4.5 showing ignition transition. Finally, a physical model is proposed to explain these results. (author)

  1. Transient response of premixed methane flames

    SciTech Connect

    Vagelopoulos, Christina M.; Frank, Jonathan H.

    2006-08-15

    The response of premixed methane-air flames to transient strain and local variations in equivalence ratio is studied during isolated interactions between a line-vortex pair and a V-flame. The temporal evolution of OH and CH is measured with planar laser-induced fluorescence for N{sub 2}-diluted flames with equivalence ratios ranging from 0.8 to 1.2. One-dimensional laminar flame calculations are used to simulate the flame response to unsteady strain and variations in reactant composition. When the reactant composition of the vortex pair and the V-flame are identical, the measurements and predictions show that the peak mole fractions of OH and CH decay monotonically in lean, stoichiometric, and rich flames. We also investigate the effects of a vortex pair with a leaner composition than the V-flame. In a stoichiometric flame, the leaner vortex enhances the decay of both OH and CH. In a rich flame, we observe an abrupt increase in OH-LIF signal and a disappearance of CH-LIF signal that are consistent with a previous experimental investigation. Our results indicate that the previously observed OH burst and CH breakage were caused by a difference in the equivalence ratios of the vortex pair and the main reactant flow. A numerical study shows that N{sub 2} dilution enhances the response of premixed flames to unsteady strain and variations in stoichiometry. Reaction-path and sensitivity analyses indicate that the peak OH and CH mole fractions exhibit significant sensitivity to the main branching reaction, H+O{sub 2} {r_reversible}OH+O. The sensitivity of OH and CH to this and other reactions is enhanced by N{sub 2} dilution. As a result, N{sub 2}-diluted flames provide a good test case for studying the reliability of chemical kinetic and transport models. (author)

  2. Studies of Premixed Laminar and Turbulent Flames at Microgravity

    NASA Technical Reports Server (NTRS)

    Ronney, Paul D.

    1993-01-01

    The work of the Principal Investigator (PI) has encompassed four topics related to the experimental and theoretical study of combustion limits in premixed flames at microgravity, as discussed in the following sections. These topics include: (1) radiation effects on premixed gas flames; (2) flame structure and stability at low Lewis number; (3) flame propagation and extinction is cylindrical tubes; and (4) experimental simulation of combustion processes using autocatalytic chemical reactions.

  3. Insulin Basics

    MedlinePlus

    ... Text Size: A A A Listen En Español Insulin Basics There are different types of insulin depending ... you may be experiencing a reaction. Types of Insulin Rapid-acting insulin , begins to work about 15 ...

  4. Insulin Secretagogues

    MedlinePlus

    ... Your Body in Balance › Insulin Secretagogues Fact Sheet Insulin Secretagogues March, 2012 Download PDFs English Espanol Editors ... medicines can help you stay healthy. What are insulin secretagogues? Insulin secretagogues (pronounced seh-KREET-ah-gogs) ...

  5. Premixes production for synthesis of wear-resistant composite materials

    NASA Astrophysics Data System (ADS)

    Kontsevoi, Yu V.; Meilakh, A. G.; Shubin, A. B.; Pastukhov, E. A.; Dolmatov, A. V.; Sipatov, I. S.

    2017-01-01

    State of the art line of powder metallurgy is application of initial powders as micro-composites with additional components - premixes. Usage of premixes inhibits segregation of added components and implies the homogeneity of powder charge composition, and finally it has a significant impact on structure formation and properties of end products. The aim of the present work was to design the new production technology of premixes based on iron powder which is layer-by-layer plated by aluminium and copper. We propose to carry out production of Cu-Al-Fe premixes in two stages: cladding of iron powder by aluminium and coating of the obtained composite by copper. The self-developed technique of vibration treatment of iron and aluminium powder mixture was chosen for this purpose. The uniform in thickness and unbroken copper-plating of Fe-Al powders were carried out by chemical technique. Physico-chemical properties and production conditions of premixes-powders were studied, besides optimal parameters of production and further heat-treatment were selected. In the result of the present study the Fe-Al-Cu premixes with laminated structure comprising of iron core, Fe-Al and Cu-Al intermetallide shells were synthesised.

  6. Fully Premixed Low Emission, High Pressure Multi-Fuel Burner

    NASA Technical Reports Server (NTRS)

    Nguyen, Quang-Viet (Inventor)

    2012-01-01

    A low-emissions high-pressure multi-fuel burner includes a fuel inlet, for receiving a fuel, an oxidizer inlet, for receiving an oxidizer gas, an injector plate, having a plurality of nozzles that are aligned with premix face of the injector plate, the plurality of nozzles in communication with the fuel and oxidizer inlets and each nozzle providing flow for one of the fuel and the oxidizer gas and an impingement-cooled face, parallel to the premix face of the injector plate and forming a micro-premix chamber between the impingement-cooled face and the in injector face. The fuel and the oxidizer gas are mixed in the micro-premix chamber through impingement-enhanced mixing of flows of the fuel and the oxidizer gas. The burner can be used for low-emissions fuel-lean fully-premixed, or fuel-rich fully-premixed hydrogen-air combustion, or for combustion with other gases such as methane or other hydrocarbons, or even liquid fuels.

  7. Premixer Design for High Hydrogen Fuels

    SciTech Connect

    Benjamin P. Lacy; Keith R. McManus; Balachandar Varatharajan; Biswadip Shome

    2005-12-16

    This 21-month project translated DLN technology to the unique properties of high hydrogen content IGCC fuels, and yielded designs in preparation for a future testing and validation phase. Fundamental flame characterization, mixing, and flame property measurement experiments were conducted to tailor computational design tools and criteria to create a framework for predicting nozzle operability (e.g., flame stabilization, emissions, resistance to flashback/flame-holding and auto-ignition). This framework was then used to establish, rank, and evaluate potential solutions to the operability challenges of IGCC combustion. The leading contenders were studied and developed with the most promising concepts evaluated via computational fluid dynamics (CFD) modeling and using the design rules generated by the fundamental experiments, as well as using GE's combustion design tools and practices. Finally, the project scoped the necessary steps required to carry the design through mechanical and durability review, testing, and validation, towards full demonstration of this revolutionary technology. This project was carried out in three linked tasks with the following results. (1) Develop conceptual designs of premixer and down-select the promising options. This task defined the ''gap'' between existing design capabilities and the targeted range of IGCC fuel compositions and evaluated the current capability of DLN pre-mixer designs when operated at similar conditions. Two concepts (1) swirl based and (2) multiple point lean direct injection based premixers were selected via a QFD from 13 potential design concepts. (2) Carry out CFD on chosen options (1 or 2) to evaluate operability risks. This task developed the leading options down-selected in Task 1. Both a GE15 swozzle based premixer and a lean direct injection concept were examined by performing a detailed CFD study wherein the aerodynamics of the design, together with the chemical kinetics of the combustion process, were

  8. Large eddy simulation of bluff body stabilized premixed and partially premixed combustion

    NASA Astrophysics Data System (ADS)

    Porumbel, Ionut

    Large Eddy Simulation (LES) of bluff body stabilized premixed and partially premixed combustion close to the flammability limit is carried out in this thesis. The main goal of the thesis is the study of the equivalence ratio effect on flame stability and dynamics in premixed and partially premixed flames. An LES numerical algorithm able to handle the entire range of combustion regimes and equivalence ratios is developed for this purpose. The algorithm has no ad-hoc adjustable model parameters and is able to respond automatically to variations in the inflow conditions, without user intervention. Algorithm validation is achieved by conducting LES of reactive and non-reactive flow. Comparison with experimental data shows good agreement for both mean and unsteady flow properties. In the reactive flow, two scalar closure models, Eddy Break-Up (EBULES) and Linear Eddy Mixing (LEMLES), are used and compared. Over important regions, the flame lies in the Broken Reaction Zone regime. Here, the EBU model assumptions fail. In LEMLES, the reaction-diffusion equation is not filtered, but resolved on a linear domain and the model maintains validity. The flame thickness predicted by LEMLES is smaller and the flame is faster to respond to turbulent fluctuations, resulting in a more significant wrinkling of the flame surface when compared to EBULES. As a result, LEMLES captures better the subtle effects of the flame-turbulence interaction, the flame structure shows higher complexity, and the far field spreading of the wake is closer to the experimental observations. Three premixed (φ = 0.6, 0.65, and 0.75) cases are simulated. As expected, for the leaner case (φ = 0.6) the flame temperature is lower, the heat release is reduced and vorticity is stronger. As a result, the flame in this case is found to be unstable. In the rich case (φ = 0.75), the flame temperature is higher, and the spreading rate of the wake is increased due to the higher amount of heat release. The ignition

  9. Studies in premixed combustion. Progress report, November 1, 1990--October 31, 1992

    SciTech Connect

    Sivashinsky, G.I.

    1992-08-01

    This report discusses the following topics on premixed combustion: theory of turbulent flame propagation; pattern formation in premixed flames and related problems; and pattern formation in extended systems. (LSP)

  10. Premixed flame propagation in vertical tubes

    NASA Astrophysics Data System (ADS)

    Kazakov, Kirill A.

    2016-04-01

    Analytical treatment of the premixed flame propagation in vertical tubes with smooth walls is given. Using the on-shell flame description, equations for a quasi-steady flame with a small but finite front thickness are obtained and solved numerically. It is found that near the limits of inflammability, solutions describing upward flame propagation come in pairs having close propagation speeds and that the effect of gravity is to reverse the burnt gas velocity profile generated by the flame. On the basis of these results, a theory of partial flame propagation driven by a strong gravitational field is developed. A complete explanation is given of the intricate observed behavior of limit flames, including dependence of the inflammability range on the size of the combustion domain, the large distances of partial flame propagation, and the progression of flame extinction. The role of the finite front-thickness effects is discussed in detail. Also, various mechanisms governing flame acceleration in smooth tubes are identified. Acceleration of methane-air flames in open tubes is shown to be a combined effect of the hydrostatic pressure difference produced by the ambient cold air and the difference of dynamic gas pressure at the tube ends. On the other hand, a strong spontaneous acceleration of the fast methane-oxygen flames at the initial stage of their evolution in open-closed tubes is conditioned by metastability of the quasi-steady propagation regimes. An extensive comparison of the obtained results with the experimental data is made.

  11. Numerical simulation of premixed turbulent methane combustion

    SciTech Connect

    Bell, John B.; Day, Marcus S.; Grcar, Joseph F.

    2001-12-14

    In this paper we study the behavior of a premixed turbulent methane flame in three dimensions using numerical simulation. The simulations are performed using an adaptive time-dependent low Mach number combustion algorithm based on a second-order projection formulation that conserves both species mass and total enthalpy. The species and enthalpy equations are treated using an operator-split approach that incorporates stiff integration techniques for modeling detailed chemical kinetics. The methodology also incorporates a mixture model for differential diffusion. For the simulations presented here, methane chemistry and transport are modeled using the DRM-19 (19-species, 84-reaction) mechanism derived from the GRIMech-1.2 mechanism along with its associated thermodynamics and transport databases. We consider a lean flame with equivalence ratio 0.8 for two different levels of turbulent intensity. For each case we examine the basic structure of the flame including turbulent flame speed and flame surface area. The results indicate that flame wrinkling is the dominant factor leading to the increased turbulent flame speed. Joint probability distributions are computed to establish a correlation between heat release and curvature. We also investigate the effect of turbulent flame interaction on the flame chemistry. We identify specific flame intermediates that are sensitive to turbulence and explore various correlations between these species and local flame curvature. We identify different mechanisms by which turbulence modulates the chemistry of the flame.

  12. The structure of particle cloud premixed flames

    NASA Technical Reports Server (NTRS)

    Seshadri, K.; Berlad, A. L.

    1992-01-01

    The structure of premixed flames propagating in combustible systems containing uniformly distributed volatile fuel particles in an oxidizing gas mixture is analyzed. This analysis is motivated by experiments conducted at NASA Lewis Research Center on the structure of flames propagating in combustible mixtures of lycopodium particles and air. Several interesting modes of flame propagation were observed in these experiments depending on the number density and the initial size of the fuel particle. The experimental results show that steady flame propagation occurs even if the initial equivalence ratio of the combustible mixture based on the gaseous fuel available in the particles, phi sub u, is substantially larger than unity. A model is developed to explain these experimental observations. In the model, it is presumed that the fuel particles vaporize first to yield a gaseous fuel of known chemical composition which then reacts with oxygen in a one-step overall process. The activation energy of the chemical reaction is presumed to be large. The activation energy characterizing the kinetics of vaporization is also presumed to be large. The equations governing the structure of the flame were integrated numerically. It is shown that the interplay of vaporization kinetics and oxidation process can result in steady flame propagation in combustible mixtures where the value of phi sub u is substantially larger than unity. This prediction is in agreement with experimental observations.

  13. Flame front geometry in premixed turbulent flames

    SciTech Connect

    Shepherd, I.G.; Ashurst, W.T.

    1991-12-01

    Experimental and numerical determinations of flame front curvature and orientation in premixed turbulent flames are presented. The experimental data is obtained from planar, cross sectional images of stagnation point flames at high Damkoehler number. A direct numerical simulation of a constant energy flow is combined with a zero-thickness, constant density flame model to provide the numerical results. The computational domain is a 32{sup 3} cube with periodic boundary conditions. The two-dimensional curvature distributions of the experiments and numerical simulations compare well at similar q{prime}/S{sub L} values with means close to zero and marked negative skewness. At higher turbulence levels the simulations show that the distributions become symmetric about zero. These features are also found in the three dimensional distributions of curvature. The simulations support assumptions which make it possible to determine the mean direction cosines from the experimental data. This leads to a reduction of 12% in the estimated flame surface area density in the middle of the flame brush. 18 refs.

  14. Premixed Gas Combustion: An Excitable System

    NASA Technical Reports Server (NTRS)

    Pearlman, Howard

    1997-01-01

    Rotating spiral and target patterns have been observed experimentally on freely-propagating premixed gas flames in large diameter tubes at normal gravity (1-g). These modes of propagation occur in near-limit mixtures which have a Lewis number (Le, defined as the ratio of the thermal diffusivity of the cold mixture to the mass diffusivity of the scarce component into the mixture) sufficiently greater than one. However, at 1-g, buoyant flows strongly distort the flame curvature, hydrodynamics (thus stretch) and convective transport of species and heat. In turn, these alter the critical Le required for onset of instability. To isolate and better understand the mechanisms which drive the observed patterns and their dynamics, 1-g and microgravity (micro-g) experiments are being conducted to determine: (1) the structure and dynamics of the patterns, (2) a map of the critical Le and heat loss for their occurrence, (3) the relative significance of the chemical kinetics, and (4) the effect of curvature (local wave and global flame front) on wave propagation. With this in hand, we will be better prepared to discuss an additional mode, a state of 'chemical turbulence,' which seems to be the ultimate fate of many of these near-limit flames prior to extinction.

  15. Flame structure and chemiluminescence in premixed flames

    NASA Astrophysics Data System (ADS)

    Grana-Otero, Jose; Mahmoudi, Siamak

    2016-11-01

    The quantitative use of chemiluminescence requires the knowledge of the relationship between the concentration of excited species with flame properties such as the equivalency ratio, the burning rate or the heat release rate. With the aim of rigorously finding from first principles these relations we have analyzed, numerically and analytically, the distribution of the excited species OH* and CH* in steady hydrogen and methane planar premixed flames. Their mass fractions turn out to be extremely small; thus, a kinetic mechanism describing their dynamics in the flame can be obtained by simply adding the kinetic mechanism describing the excitation and de-excitation to the mechanism of the base flame. Due also to their small concentrations, the excited species are in steady state, facilitating a simple analytical description. The analyses show that OH*, both in hydrogen and methane flames, can be found broadly distributed downstream the preheat region, in a three-layer structure that is analytically described. The distribution of CH* is much simpler, being always in equilibrium with CH, whose concentration is in turn proportional to that of CH4. As a result, CH* is confined to the methane consumption layer in lean flames, but broadly distributed in rich flames.

  16. Amylin Analogues in the Treatment of Diabetes Mellitus: Medicinal Chemistry and Structural Basis of its Function

    PubMed Central

    Adeghate, Ernest; Kalász, Huba

    2011-01-01

    Amylin, (islet amyloid polypeptide) or diabetes-associated peptide is co-secreted with insulin in the islet of Langerhans of diabetic patients in approximately 1:100, amylin-insulin ratio. The soluble form of amylin, an analogue of amylin, is used as a supplement to insulin in the treatment of type 1 diabetes. Co-administration of amylin analogue with insulin to patients with type 1 diabetes induced a larger reduction in proprandial hyperglycemia, with a concomitant reduction in the level of glucagon when compared to insulin monotherapy. The actions of amylin analogues appear to be synergistic to insulin, with which it is co-released from insulin-producing beta cells after a meal. Amylin analogues such as pramlintide has been shown to significantly reduce body weight, HbA1c values and even the dosage of insulin. A moderate weight loss can also be achieved in obese patients with or without diabetes. A major side effect of some amylin analogues includes nausea and excitation of the area postrema. This review examines the medicinal chemistry of amylin and its analogues and their effects. PMID:21966328

  17. An assessment of the adequacy of suspension of insulin in pen injectors.

    PubMed

    Brown, A; Steel, J M; Duncan, C; Duncan, A; McBain, A M

    2004-06-01

    To evaluate the completeness of insulin resuspension by users of neutral Hagedorn (NPH) insulin pens and premixed insulin pens and to relate this to how patients mix insulin before injecting. Patients (n = 180) administering a medium duration or premixed insulin in cartridges in disposable pens were asked questions about mixing insulin, injection technique and storing insulin. They were also asked to demonstrate how they mixed their insulin and to send in a half-used pen. The cloudy component equates to the complexed insulin, while the clear component is the diluting fluid or soluble insulin, depending on the type of insulin used. The optical density, a simple way of measuring cloudiness, was measured in each cartridge or disposable pen and was compared with the range obtained from a series of unused control pens. The results for 146 pens containing the most commonly used insulin were included. The 21 patients whose residual pen insulins showed optical densities > 5 SD from the mean were re-interviewed and their medical records were examined in detail. Insulin in the pens was also measured by immunoassay to confirm the utility of optical density measurements. Only one patient mixed the insulin as the manufacturers recommended. In 58 out of 146 pens or cartridges (40%) the opacity of the insulin varied significantly from the expected value. Most patients in Kirkcaldy do not mix insulin adequately. This may result in their giving different incorrect doses of insulin during the use of each pen. More emphasis should be given to teaching patients to mix correctly.

  18. A filtered tabulated chemistry model for LES of premixed combustion

    SciTech Connect

    Fiorina, B.; Auzillon, P.; Darabiha, N.; Gicquel, O.; Veynante, D.; Vicquelin, R.

    2010-03-15

    A new modeling strategy called F-TACLES (Filtered Tabulated Chemistry for Large Eddy Simulation) is developed to introduce tabulated chemistry methods in Large Eddy Simulation (LES) of turbulent premixed combustion. The objective is to recover the correct laminar flame propagation speed of the filtered flame front when subgrid scale turbulence vanishes as LES should tend toward Direct Numerical Simulation (DNS). The filtered flame structure is mapped using 1-D filtered laminar premixed flames. Closure of the filtered progress variable and the energy balance equations are carefully addressed in a fully compressible formulation. The methodology is first applied to 1-D filtered laminar flames, showing the ability of the model to recover the laminar flame speed and the correct chemical structure when the flame wrinkling is completely resolved. The model is then extended to turbulent combustion regimes by including subgrid scale wrinkling effects in the flame front propagation. Finally, preliminary tests of LES in a 3-D turbulent premixed flame are performed. (author)

  19. Annular fuel and air co-flow premixer

    DOEpatents

    Stevenson, Christian Xavier; Melton, Patrick Benedict; York, William David

    2013-10-15

    Disclosed is a premixer for a combustor including an annular outer shell and an annular inner shell. The inner shell defines an inner flow channel inside of the inner shell and is located to define an outer flow channel between the outer shell and the inner shell. A fuel discharge annulus is located between the outer flow channel and the inner flow channel and is configured to inject a fuel flow into a mixing area in a direction substantially parallel to an outer airflow through the outer flow channel and an inner flow through the inner flow channel. Further disclosed are a combustor including a plurality of premixers and a method of premixing air and fuel in a combustor.

  20. Insulin Test

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Insulin Share this page: Was this page helpful? Also known as: Fasting Insulin Formal name: Insulin, serum Related tests: C-peptide , ...

  1. Acoustic radiation from weakly wrinkled premixed flames

    SciTech Connect

    Lieuwen, Tim; Mohan, Sripathi; Rajaram, Rajesh; Preetham,

    2006-01-01

    This paper describes a theoretical analysis of acoustic radiation from weakly wrinkled (i.e., u'/S{sub L}<1) premixed flames. Specifically, it determines the transfer function relating the spectrum of the acoustic pressure oscillations, P'({omega}), to that of the turbulent velocity fluctuations in the approach flow, U'({omega}). In the weakly wrinkled limit, this transfer function is local in frequency space; i.e., velocity fluctuations at a frequency {omega} distort the flame and generate sound at the same frequency. This transfer function primarily depends upon the flame Strouhal number St (based on mean flow velocity and flame length) and the correlation length, {lambda}, of the flow fluctuations. For cases where the ratio of the correlation length and duct radius {lambda}/a>>1, the acoustic pressure and turbulent velocity power spectra are related by P'({omega})-{omega}{sup 2}U'({omega}) and P'({omega})-U'({omega}) for St<<1 and St>>1, respectively. For cases where {lambda}/a<<1, the transfer functions take the form P'({omega})-{omega}{sup 2}({lambda}/a){sup 2}U'({omega}) and P'({omega})-{omega}{sup 2}({lambda}/a){sup 2}({psi}-{delta}ln({lambda}/a))U'({omega}) for St<<1 and St>>1, respectively, where (PS) and {delta} are constants. The latter result demonstrates that this transfer function does not exhibit a simple power law relationship in the high frequency region of the spectra. The simultaneous dependence of this pressure-velocity transfer function upon the Strouhal number and correlation length suggests a mechanism for the experimentally observed maximum in acoustic spectra and provides some insight into the controversy in the literature over how this peak should scale with the flame Strouhal number.

  2. Combustion-acoustic stability analysis for premixed gas turbine combustors

    NASA Technical Reports Server (NTRS)

    Darling, Douglas; Radhakrishnan, Krishnan; Oyediran, Ayo; Cowan, Lizabeth

    1995-01-01

    Lean, prevaporized, premixed combustors are susceptible to combustion-acoustic instabilities. A model was developed to predict eigenvalues of axial modes for combustion-acoustic interactions in a premixed combustor. This work extends previous work by including variable area and detailed chemical kinetics mechanisms, using the code LSENS. Thus the acoustic equations could be integrated through the flame zone. Linear perturbations were made of the continuity, momentum, energy, chemical species, and state equations. The qualitative accuracy of our approach was checked by examining its predictions for various unsteady heat release rate models. Perturbations in fuel flow rate are currently being added to the model.

  3. Insulin degludec and insulin degludec/insulin aspart in Ramadan: A single center experience

    PubMed Central

    Kalra, Sanjay

    2016-01-01

    This study aimed to document the utility and safety of insulin degludec (IDeg) and insulin degludec aspart (IDegAsp) in persons with type 2 diabetes, observing the Ramadan fast. An observational study was conducted at a single center, in the real world setting, on six persons who either switched to IDeg or IDegAsp a month before Ramadan or changed time of administration of IDegAsp at the onset of Ramadan, to keep the fast in a safe manner. Subjects were kept under regular monitoring and surveillance before, during, and after Ramadan, and counseled in an opposite manner. Four persons, who shifted from premixed insulin to IDegAsp, experienced a 12–18% dose reduction after 14 days. At the onset of Ramadan, the Suhur dose was reduced by 30%, and this remained unchanged during the fasting month. The Iftar dose had to be increased by 4 units. One person who shifted from neutral protamine hagedorn to IDeg demonstrated a 25% dose reduction at 20 days, without any further change in insulin requirement during Ramadan. One person who changed time of injection of IDegAsp from morning to night reported no change in dosage. No episode of major hypoglycemia was reported. IDeg and IDegAsp are effective, safe, and well-tolerated means of achieving glycemic control in persons with type 2 diabetes who wish to fast. PMID:27366727

  4. Premixing and flash vaporization in a two-stage combustor

    SciTech Connect

    Sjoblom, B.G.A.

    1982-01-01

    A double recirculation zone two-stage combustor fitted with airblast atomizers has been investigated in a previous work. This paper describes further tests with premixing tubes in the secondary combustion zone. Flash vaporization was employed to ensure complete vaporization of the secondary fuel, which was heated to 600K by the combustor inlet air. 9 refs.

  5. The quest for physiologic insulin replacement.

    PubMed

    Owens, David R

    2004-11-01

    Historically, the objective of insulin replacement has been to simulate the 2 major components of insulin secretion in individuals without diabetes mellitus: the low-level basal secretion during the night and periods of fasting, and the prandial secretion in response to food intake. The variable pharmacokinetic and pharmacodynamic characteristics of conventional insulin preparations have made mimicking these physiologic profiles virtually impossible. Balancing the effects of diet, exercise, and the numerous factors contributing to intra- and inter-individual variations in insulin absorption and action, such as type, site of injection, and dosage of insulin, while avoiding the very serious side effect of hypoglycemia in seeking normoglycemia, presents a further challenge. Recently, these limitations have been addressed by recombinant DNA-mediated development of insulin analogues, such as rapid-acting insulin lispro, aspart and glulisine, and the long-acting insulin preparations, insulin glargine and detemir. The molecular structures of these analogues have produced time-action profiles that better approach prandial and basal insulin secretion, thus allowing for easier, safer, and more flexible treatment regimens.

  6. [Introduction of mutations in insulin molecule: positive and negative mutations].

    PubMed

    Ksenofontova, O I

    2014-01-01

    Introduction of mutations in an insulin molecule is one of the important approaches to drug development for treatment of diabetes mellitus. Generally, usage of mutations is aimed at activation of insulin and insulin receptor interaction. Such mutations can be considered as positive. Mutations that reduce the binding efficacy are negative. There are neutral mutations as well. This article considers both natural mutations that are typical for various members of the insulin superfamily and artificial ones which are introduced to improve the insulin pharmacological characteristics. Data presented here can be useful in developing new effective insulin analogues for treatment of diabetes mellitus.

  7. Insulin signaling and insulin resistance.

    PubMed

    Beale, Elmus G

    2013-01-01

    Insulin resistance or its sequelae may be the common etiology of maladies associated with metabolic syndrome (eg, hypertension, type 2 diabetes, atherosclerosis, heart attack, stroke, and kidney failure). It is thus important to understand those factors that affect insulin sensitivity. This review stems from the surprising discovery that interference with angiotensin signaling improves insulin sensitivity, and it provides a general overview of insulin action and factors that control insulin sensitivity.

  8. Insulin and Lispro Insulin: What is Common and Different in their Behavior?

    PubMed

    Selivanova, Olga M; Suvorina, Mariya Yu; Surin, Alexey K; Dovidchenko, Nikita V; Galzitskaya, Oxana V

    2017-01-01

    There are different insulin analogues with various pharmacokinetic characteristics, such as, rapid-acting, long-acting, or intermediate-acting analogues. Since insulin tends to form amyloid aggregates, it is of particular interest to measure characteristic times of formation of amyloid aggregates and compare those to action times for insulin and its analogues. For the study we have chosen one of the insulin analogues - insulin Lispro, which is a fast acting insulin analog. It is usually thought of amyloid aggregation as a nucleation-dependent process. We have estimated the size of the primary nucleus to be one monomer and the size of the secondary nucleus to be around zero in both insulin and Lispro insulin aggregation processes. The main structural element of insulin and Lispro insulin amyloid fibrils is a rounded ring oligomer of about 6-7 nm in diameter, about 2-3 nm in height and about 2 nm in diameter of the hole. Fibrils of several μm in length are produced due to interaction of such oligomers. The packing of ring oligomers in fibrils differs because of the difference in their orderliness. Though the initial stages of fibril formation (monomer, oligomer) are similar, the further process depends on the unique sequence of each peptide. Namely the sequence affects the final morphology of mature amyloids. These observations allow us to conclude that formation of fibrils by short peptides occurs via and by means of oligomer ring structures. Such an important issue as the nature of polymorphism of insulin amyloid fibrils has been settled by us. The role of early oligomeric aggregates in such processes as nucleation and aggregation of amyloid fibrils has been examined.

  9. Survey of Analogue Spacetimes

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    Analogue spacetimes (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole,(mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid—and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  10. Development of insulin allergy after bone marrow transplantation.

    PubMed

    Yoshida, N; Okubo, M; Ishiguro, K; Mori, Y

    2012-10-01

    Insulin allergy is a not uncommon condition even though human insulin and insulin analogues are widely used. However, the development of insulin allergy after bone marrow transplantation has not been reported. A 44-year-old Japanese woman had aplastic anaemia and secondary haemochromatosis. She was diagnosed with having diabetes at age 32 years and had been treated with human insulin. At age 34 years, bone marrow transplantation was performed. One year later, a rash and urticaria appeared immediately after insulin injections. Intracutaneous tests were positive for both human insulins and analogues, whereas the test for protamine was negative. Furthermore, an IgE-radioallergosorbent test against insulin was positive. Thus, we diagnosed the patient with having an IgE-mediated type I allergy against insulin. Insulin therapy with insulin aspart, which showed the least skin reaction, was continued and the insulin allergy disappeared in 7 years. This is the first description of insulin allergy after bone marrow transplantation. Our case underscores the effects of bone marrow cells on IgE-mediated type I allergy for insulin. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

  11. Inhaled insulin: a breath of fresh air? A review of inhaled insulin.

    PubMed

    Santos Cavaiola, Tricia; Edelman, Steven

    2014-08-01

    Despite many advances in diabetes care over the last century, some elements of insulin therapy remain inadequate for optimal care of the patient with diabetes. There is a need for improved pharmacokinetics and pharmacodynamics of rapid-acting insulin analogues to mimic physiologic insulin secretion. In addition, a major barrier to successful insulin therapy has been patient resistance. Alternative routes of insulin administration, including inhaled insulin, have been under investigation for several years. This review discusses the rationale for pulmonary delivery of insulin, compares previous inhaled insulin products, reviews the literature on the safety and efficacy of a current inhaled insulin formulation under investigation, and compares this product with other prandial insulin products. English-language studies and reviews of inhaled insulin were searched in MEDLINE, the ClinicalTrials.gov registry (through May 2014), and the US Food and Drug Administration Website. Inhaled insulin has several favorable characteristics due to pulmonary anatomy/physiology and the lack of injections. Pharmacokinetic and pharmacodynamic studies have shown a time-action profile suitable for prandial insulin use. Inhaled insulin seems to be safe and effective compared with other prandial insulin products and may be preferable to subcutaneous rapid-acting insulin analogues in terms of time-action profiles and rates of hypoglycemia. Small decreases in forced expiratory volume in 1 second (FEV1) have been shown with inhaled insulin, although this finding is not progressive over time and reverses with cessation of the medication. Although several inhaled insulin products have been under investigation, only one (Exubera(®) [Nektar Therapeutics, San Carlos, California/Pfizer Inc, New York, New York]) was approved by the US Food and Drug Administration, and it was pulled from the market after only a short period of time. Technosphere(®) insulin (MannKind Corporation, Valencia, California

  12. New forms of insulin and insulin therapies for the treatment of type 2 diabetes.

    PubMed

    Cahn, Avivit; Miccoli, Roberto; Dardano, Angela; Del Prato, Stefano

    2015-08-01

    Insulin is a common treatment option for many patients with type 2 diabetes, and is generally used late in the natural history of the disease. Its injectable delivery mode, propensity for weight gain and hypoglycaemia, and the paucity of trials assessing the risk-to-safety ratio of early insulin use are major shortcomings associated with its use in patients with type 2 diabetes. Development of new insulins-such as insulin analogues, including long-acting and short-acting insulins-now provide alternative treatment options to human insulin. These novel insulin formulations and innovative insulin delivery methods, such as oral or inhaled insulin, have been developed with the aim to reduce insulin-associated hypoglycaemia, lower intraindividual pharmacokinetic and pharmacodynamic variability, and improve imitation of physiological insulin release. Availability of newer glucose-lowering drugs (such as glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose co-transporter-2 inhibitors) also offers the opportunity for combination treatment; the results of the first trials in this area of research suggest that such treatment might lead to use of reduced insulin doses, less weight gain, and fewer hypoglycaemic episodes than insulin treatment alone. These and future developments will hopefully offer better opportunities for individualisation of insulin treatment for patients with type 2 diabetes.

  13. Relationship between insulin A chain regions and insulin biological activities

    PubMed Central

    Yang, Shi-Zhen; Huang, Yi-Ding; Jie, Xin-Feng; Feng, You-Min; Niu, Jing-Yi

    2000-01-01

    AIM: To study the relationship between insulin A chain regions and insulin biological activities, we designed a series of insulin analogues with changes at A21, A12-18 of C-terminal helical region and A8-10 located in the region of A6-A11 intra-chain disulphide bond. METHODS: Insulin A-chain analogues were prepared by stepwise Fmoc solid-phase manual synthesis and then combined with natural B-chain of porcine insulin to yield corresponding insulin analogues. Their biological activities were tested by receptor binding, mouse convulsion and immunological assay. RESULTS: [A21Ala]Ins retains 70.3% receptor binding capacity and 60% in vivo biological activity. [DesA13-14, A21Ala]Ins and [DesA12-13-14-15, A21Ala] Ins still have definite biological activity, 7.9% and 4.0% receptor binding, and 6.2% and 3.3% in vivo biological activity respectively. [A15Asn, A17Pro, A21Ala]Ins maintains 10.4% receptor binding and 10% in vivo biological activity. [A8His, A9Arg, A10Pro, A21Ala]Ins, [A8His, A9Lys, A10Pro, A21Ala]Ins and [A8His, A9Lys, A10Arg, A21Ala]Ins have 51.9%, 44.3% and 32.1% receptor binding respectively, 50%, 40% and 30% in vivo biological activity respectively, and 28.8%, 29.6% and 15.4% immunological activity respectively. CONCLUSION: A21Asn can be replaced by simple amino acid residues. The A chains with gradually damaged structur al integrity in A12-18 helical region and the demolition of the A12-18 helical region by the substitution of Pro and Asn for A17Glu and A15Gln respectively ca n combine with the B chain and the combination products show definite biological activity, the helical structure of A12-18 is essential for biological activities of insulin. A8-10 is not much concerned with biological activities, but is much more important antigenically in binding to its antibodies, these results may help us design a new type of insulin analogue molecule. PMID:11819600

  14. Insulin adherence and persistence among Chinese patients with type 2 diabetes: a retrospective database analysis

    PubMed Central

    He, Xiaoning; Chen, Liming; Wang, Ke; Wu, Haiya; Wu, Jing

    2017-01-01

    Objective To assess adherence and persistence to insulin therapy and identify its associated factors among Chinese insulin-naïve patients with type 2 diabetes (T2D). Methods Tianjin Urban Employee Basic Medical Insurance claims database was used (2008–2011). Adult patients with T2D who initiated insulin therapy during January 2009 through December 2010 and were continuously enrolled for 12 months pre-(baseline) and 12 months post-initiation (follow-up) were included. Patients who had a ≥80% medication possession ratio were deemed adherent, while patients who had no gaps of ≥90 days in insulin therapy were deemed persistent. Associated factors of insulin adherence and persistence were detected by univariate and multivariate analyses. Results A total of 24,192 patients were included; the patients had a mean age of 58.9 years, with 49.5% being female. About 51.9% of the patients had human insulin as initiation therapy, while 39.1% were initiated with insulin analog and 9.0% with animal-derived insulin. Premixed insulin (77.3%) was prescribed most often in comparison with basal (11.8%) and prandial (10.9%) insulin. Only 30.9% of patients were adherent, and the mean (standard deviation) medication possession ratio was 0.499 (0.361). About 53.0% of patients persisted insulin therapy during follow-up, and the mean time to nonpersistence was 230.3 (145.5) days. Patients initiated with analog were more likely to be adherent (adjusted odds ratio: 1.07, P=0.036) and persistent (adjusted hazard ratio: 0.88, P<0.001) compared with those initiated with human insulin. Patients initiation with basal insulin had lower adherence relative to premixed (adjusted odds ratio: 0.79, P<0.001). Patients comorbid with hypertension or dyslipidemia, initiated with prandial insulin, and with baseline severe hypoglycemic events were more likely to be nonadherent/nonpersistent. Conclusion The insulin adherence and persistence among Chinese patients with T2D are generally poor. Initiation

  15. CHALLENGES WITH INSULIN USE AMONG PATIENTS WITH TYPE 2 DIABETES MELLITUS: FOCUS ON A TERTIARY HEALTHCARE SETTING IN SOUTH-EAST NIGERIA.

    PubMed

    Ezeani Ignatius, U; Onyeonoro Ugochukwu, U; Ugwu Theophilus, E; Chuku, Abali; Aihanuwa, Eregie

    2015-10-16

    Effective usage of insulin in the management of diabetes remains a challenge in developing countries like Nigeria. The objective of this study is to document the pattern of insulin prescription, frequency, storage, common regimen used, and attendant problems associated with its use in patients with type 2 diabetes mellitus (T2DM). This was a prospective, descriptive study in which consecutive T2DM patients seen at the medical out-patient clinic and medical wards and who fulfilled the criteria for inclusion were recruited. Participants provided information on their demographic characteristics, diabetes history, treatment and problems associated with treatment, type of insulin in use, number of daily injections, storage, method of insulin administration and problems associated with insulin use. Clinical examination was carried out basically to determine the anthropometric indices. about 84.3% have used insulin for less than 5 years. The thigh was the commonest site of insulin administration (95.3%). About 94.3% of subjects in this study store their insulin in a refrigerator. And Insulin dosing regimen ranged from less than once to four times daily while majority of patients (63%) were on twice daily insulin regimen. Insulin administration devices used were Insulin syringes 394 (98.5%) and Insulin pens 6 (1.5%). Thirty three percent of the subjects self inject insulin while about half of the study subjects (50.5%) receive insulin from a healthcare provider. The most common insulin used by patients was Mixed/ Premixed insulin (32.8%) and Regular/ Soluble insulin (38.8%). Hypoglycaemia was the most frequently documented problem encountered by subjects on insulin followed by weight gain. Majority of the study subjects (50.8%) practice self monitoring of blood glucose (SMBG). This study has demonstrated that majority of subjects with T2DM were on premixed insulin and that hypoglycaemia is the most common problem reported by patients. Insulin pens were not common among our

  16. Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the Southwest Saudi Arabia cohort of the A1chieve study

    PubMed Central

    Shawkat, Waffaa; Abdou, Magdy; Ghannam, Nadia; Mahfouz, Ashraf Shaaban

    2013-01-01

    Background: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. Materials and Methods: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from southwest Saudi Arabia. Results: A total of 2561 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Study patients had started on or were switched to biphasic insulin aspart (n = 987), insulin detemir (n = 1121), insulin aspart (n = 21), basal insulin plus insulin aspart (n = 280) and missing or other insulin combinations (n = 152). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.9%) and insulin user (mean HbA1c: 9.5%) groups. After 24 weeks of treatment, both the study groups showed improvement in HbA1c (insulin naïve: −2.5%, insulin users: −2.2%). Major hypoglycaemic events did not occur in any of the study patients. SADRs were reported in 0.1% of insulin naïve and 0.1% of insulin user groups. Conclusion: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia. PMID:24404479

  17. Effects of LY117018 and the estrogen analogue, 17alpha-ethinylestradiol, on vascular reactivity, platelet aggregation, and lipid metabolism in the insulin-resistant JCR:LA-cp male rat: role of nitric oxide.

    PubMed

    Russell, J C; McKendrick, J D; Dubé, P J; Dolphin, P J; Radomski, M W

    2001-01-01

    The JCR:LA-cp rat is obese and insulin resistant and develops a major vasculopathy, with associated ischemic damage to the heart. Male rats were treated with 17alpha-ethinylestradiol (EE), LY117018, and/or the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME). LY117018 decreased plasma cholesterol esters, with a 40% reduction in total cholesterol. EE increased triglyceride levels and modestly decreased cholesterol esters. L-NAME increased blood pressure and aortic contractile sensitivity to phenylephrine and inhibited acetylcholine-induced relaxation. LY117018 decreased the force of contraction. The L-NAME-mediated increase in force of contraction and decrease in response to acetylcholine was inhibited by LY117018. L-NAME-induced hypertension was prevented by LY117018. Platelet aggregation was not different between obese and lean rats and was unaffected by L-NAME. LY117018, both in the absence and presence of L-NAME, inhibited platelet aggregation. The effects of LY117018 are apparently mediated through both NO-dependent and -independent mechanisms. The changes induced by EE and LY117018 may reflect the activation of multiple mechanisms, both estrogen receptor-dependent and -independent. The changes induced by LY117018 are significant and may prove to be cardioprotective in the presence of the insulin resistance syndrome.

  18. Premixing quality and flame stability: A theoretical and experimental study

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, K.; Heywood, J. B.; Tabaczynski, R. J.

    1979-01-01

    Models for predicting flame ignition and blowout in a combustor primary zone are presented. A correlation for the blowoff velocity of premixed turbulent flames is developed using the basic quantities of turbulent flow, and the laminar flame speed. A statistical model employing a Monte Carlo calculation procedure is developed to account for nonuniformities in a combustor primary zone. An overall kinetic rate equation is used to describe the fuel oxidation process. The model is used to predict the lean ignition and blow out limits of premixed turbulent flames; the effects of mixture nonuniformity on the lean ignition limit are explored using an assumed distribution of fuel-air ratios. Data on the effects of variations in inlet temperature, reference velocity and mixture uniformity on the lean ignition and blowout limits of gaseous propane-air flames are presented.

  19. Commercial premixed parenteral nutrition: Is it right for your institution?

    PubMed

    Miller, Sarah J

    2009-01-01

    Two-compartment premixed parenteral nutrition (PN) products are heavily promoted in the United States. These products may present safety advantages over PN solutions mixed by a local pharmacy, although clinical data to support this assertion are scarce. Multicompartment products can be labor-saving for pharmacy and therefore may be cost-effective for some institutions. Before adopting such products for use, an institution must determine that standardized PN solutions are acceptable for many or most of their patients compared with customized PN compounded specifically for individual patients. A larger selection of premixed products is available in Europe and some other parts of the world compared with the United States. Availability of a broader selection of products in the United States, including 3-compartment bags and a wider range of macronutrient concentrations and volumes, may make the use of such products more desirable in the future.

  20. Partially Premixed Flame (PPF) Research for Fire Safety

    NASA Technical Reports Server (NTRS)

    Puri, Ishwar K.; Aggarwal, Suresh K.; Lock, Andrew J.; Hegde, Uday

    2004-01-01

    Incipient fires typically occur after the partial premixing of fuel and oxidizer. The mixing of product species into the fuel/oxidizer mixture influences flame stabilization and fire spread. Therefore, it is important to characterize the impact of different levels of fuel/oxidizer/product mixing on flame stabilization, liftoff and extinguishment under different gravity conditions. With regard to fire protection, the agent concentration required to achieve flame suppression is an important consideration. The initial stage of an unwanted fire in a microgravity environment will depend on the level of partial premixing and the local conditions such as air currents generated by the fire itself and any forced ventilation (that influence agent and product mixing into the fire). The motivation of our investigation is to characterize these impacts in a systematic and fundamental manner.

  1. Pulsed jet combustion generator for non-premixed charge engines

    DOEpatents

    Oppenheim, A. K.; Stewart, H. E.

    1990-01-01

    A device for introducing fuel into the head space of cylinder of non-premixed charge (diesel) engines is disclosed, which distributes fuel in atomized form in a plume, whose fluid dynamic properties are such that the compression heated air in the cylinder head space is entrained into the interior of the plume where it is mixed with and ignites the fuel in the plume interior, to thereby control combustion, particularly by use of a multiplicity of individually controllable devices per cylinder.

  2. Lean, Premixed-Prevaporized (LPP) combustor conceptual design study

    NASA Technical Reports Server (NTRS)

    Dickman, R. A.; Dodds, W. J.; Ekstedt, E. E.

    1979-01-01

    Four combustion systems were designed and sized for the energy efficient engine. A fifth combustor was designed for the cycle and envelope of the twin-spool, high bypass ratio, high pressure ratio turbofan engine. Emission levels, combustion performance, life, and reliability assessments were made for these five combustion systems. Results of these design studies indicate that cruise NOx emission can be reduced by the use of lean, premixed-prevaporaized combustion and airflow modulation.

  3. Premixed burner experiments: Geometry, mixing, and flame structure issues

    SciTech Connect

    Gupta, A.K.; Lewis, M.J.; Gupta, M.

    1995-10-01

    This research program is exploring techniques for improved fuel-air mixing, with the aim of achieving combustor operations up to stoichiometric conditions with minimal NO x and maximum efficiency. The experimental studies involve the use of a double-concentric natural gas burner that is operable in either premixed or non-premixed modes, and the system allows systematic variation of equivalence ratio, swirl strength shear length region and flow momentum in each annulus. Flame structures formed with various combinations of swirl strengths, flow throughput and equivalence ratios in premixed mode show the significant impact of swirl flow distribution on flame structure emanating from the mixedness. This impact on flame structure is expected to have a pronounced effect on the heat release rate and the emission of NO{sub x}. Thus, swirler design and configuration remains a key factor in the quest for completely optimized combustion. Parallel numerical studies of the flow and combustion phenomena were carried out, using the RSM and thek-{epsilon} turbulence models. These results have not only indicated the strengths and limitations of CFD in performance and pollutants emission predictions, but have provided guidelines on the size and strength of the recirculation produced and the spatio-temporal structure of the combustion flowfield. The first stage of parametric studies on geometry and operational parameters at Morgan State University have culminated in the completion of a one-dimensional flow code that is integrated with a solid, virtual model of the existing premixed burner. This coupling will provide the unique opportunity to study the impact of geometry on the flowfield and vice-versa, with particular emphasis on concurrent design optimization.

  4. [Insulin signaling and insulin resistance].

    PubMed

    Ferré, Pascal

    2007-01-01

    Insulin controls carbohydrate and lipid metabolism. Among other things, it stimulates glucose storage as glycogen and lipid storage as triglycerides. Insulin acts through a membrane receptor which is a tyrosine kinase. When activated by insulin binding, the tyrosine kinase will recruit and phosphorylate intracellular substrates called IRS (insulin receptor substrate). Phosphorylated IRS will be used as docking sites for proteins which will transmit the insulin signal through several systems (e.g. PI3-kinase). The insulin resistance which is concomitant with type 2 diabetes and obesity is linked to an increased intracellular availability of fatty acids which are precursors of lipid mediators inducing a decreased efficiency of insulin signal transmission. Therapies aimed at improving insulin sensitivity could then target proteins involved in the regulation of intacellular fatty acid availibility.

  5. Large eddy simulation of unsteady lean stratified premixed combustion

    SciTech Connect

    Duwig, C.; Fureby, C.

    2007-10-15

    Premixed turbulent flame-based technologies are rapidly growing in importance, with applications to modern clean combustion devices for both power generation and aeropropulsion. However, the gain in decreasing harmful emissions might be canceled by rising combustion instabilities. Unwanted unsteady flame phenomena that might even destroy the whole device have been widely reported and are subject to intensive studies. In the present paper, we use unsteady numerical tools for simulating an unsteady and well-documented flame. Computations were performed for nonreacting, perfectly premixed and stratified premixed cases using two different numerical codes and different large-eddy-simulation-based flamelet models. Nonreacting simulations are shown to agree well with experimental data, with the LES results capturing the mean features (symmetry breaking) as well as the fluctuation level of the turbulent flow. For reacting cases, the uncertainty induced by the time-averaging technique limited the comparisons. Given an estimate of the uncertainty, the numerical results were found to reproduce well the experimental data in terms both of mean flow field and of fluctuation levels. In addition, it was found that despite relying on different assumptions/simplifications, both numerical tools lead to similar predictions, giving confidence in the results. Moreover, we studied the flame dynamics and particularly the response to a periodic pulsation. We found that above a certain excitation level, the flame dynamic changes and becomes rather insensitive to the excitation/instability amplitude. Conclusions regarding the self-growth of thermoacoustic waves were drawn. (author)

  6. The nonlinear behaviour of a ducted premixed flame

    NASA Astrophysics Data System (ADS)

    Kashinath, Karthik; Waugh, Iain; Hemchandra, Santosh; Juniper, Matthew

    2012-11-01

    Nonlinear thermoacoustic oscillations are one of the most challenging problems in premixed gas turbine engine combustors. We investigate the nonlinear thermoacoustic behaviour of a ducted premixed flame using two approaches:(i) a matrix-free continuation analysis in the time domain; and (ii) a quasi-linear flame describing function (FDF) approach in the frequency domain. Continuation methods find limit cycles numerically in the time domain and track them as the operating condition of the system changes, with no additional assumptions other than those used to form the governing equations. The FDF characterizes the flame's response to harmonic velocity fluctuations over a range of forcing frequencies and forcing amplitudes. Limit cycles can then be found using an integral criterion derived from the acoustic momentum and energy equations. The gain and phase of the FDF, combined with the limit cycles and floquet modes obtained from the continuation analysis reveal physical information about the flame-acoustic interaction. We use these approaches on a model of a ducted premixed flame, to show how the bifurcation surfaces of this thermoacoustic system can be calculated over a large parameter space, as well as how the physical mechanisms causing these bifurcations may be identified. Supported by EPSRC and Rolls Royce.

  7. Computations of turbulent lean premixed combustion using conditional moment closure

    NASA Astrophysics Data System (ADS)

    Amzin, Shokri; Swaminathan, Nedunchezhian

    2013-12-01

    Conditional Moment Closure (CMC) is a suitable method for predicting scalars such as carbon monoxide with slow chemical time scales in turbulent combustion. Although this method has been successfully applied to non-premixed combustion, its application to lean premixed combustion is rare. In this study the CMC method is used to compute piloted lean premixed combustion in a distributed combustion regime. The conditional scalar dissipation rate of the conditioning scalar, the progress variable, is closed using an algebraic model and turbulence is modelled using the standard k-ɛ model. The conditional mean reaction rate is closed using a first order CMC closure with the GRI-3.0 chemical mechanism to represent the chemical kinetics of methane oxidation. The PDF of the progress variable is obtained using a presumed shape with the Beta function. The computed results are compared with the experimental measurements and earlier computations using the transported PDF approach. The results show reasonable agreement with the experimental measurements and are consistent with the transported PDF computations. When the compounded effects of shear-turbulence and flame are strong, second order closures may be required for the CMC.

  8. Spectral Kinetic Energy Transfer Through a Premixed Flame Brush

    NASA Astrophysics Data System (ADS)

    Towery, Colin A. Z.; Poludnenko, Alexei Y.; Hamlington, Peter E.

    2014-11-01

    Turbulence-flame interactions are of fundamental importance for understanding and modeling premixed turbulent reacting flows. These interactions can result in nonlinear feedback leading to large changes in both the turbulence and flame. Recent computational studies have indicated, however, that not all scales of turbulent motion are affected equally. Small-scale motions appear to be suppressed while larger-scale motions are unaffected or even enhanced. In order to determine the scale-dependence of turbulence-flame interactions, direct numerical simulations of statistically planar, premixed flames have been performed and analyzed. Two-dimensional kinetic energy spectra, conditioned on the planar-averaged fuel mass-fraction, are measured through the flame brush and compared to both compressible and incompressible non-reacting flow spectra. Changes in the spectra with respect to fuel mass-fraction are then connected to the dynamics of the kinetic energy spectrum transport equation. Particular focus is placed on understanding triadic velocity, pressure, and dilatation interactions, including the characterization of backscatter due to heat release and compressibility. Finally, the implications of these results for modeling practical premixed combustion problems are outlined.

  9. Spectral kinetic energy transfer in turbulent premixed reacting flows.

    PubMed

    Towery, C A Z; Poludnenko, A Y; Urzay, J; O'Brien, J; Ihme, M; Hamlington, P E

    2016-05-01

    Spectral kinetic energy transfer by advective processes in turbulent premixed reacting flows is examined using data from a direct numerical simulation of a statistically planar turbulent premixed flame. Two-dimensional turbulence kinetic-energy spectra conditioned on the planar-averaged reactant mass fraction are computed through the flame brush and variations in the spectra are connected to terms in the spectral kinetic energy transport equation. Conditional kinetic energy spectra show that turbulent small-scale motions are suppressed in the burnt combustion products, while the energy content of the mean flow increases. An analysis of spectral kinetic energy transfer further indicates that, contrary to the net down-scale transfer of energy found in the unburnt reactants, advective processes transfer energy from small to large scales in the flame brush close to the products. Triadic interactions calculated through the flame brush show that this net up-scale transfer of energy occurs primarily at spatial scales near the laminar flame thermal width. The present results thus indicate that advective processes in premixed reacting flows contribute to energy backscatter near the scale of the flame.

  10. Premixed intravenous admixtures: a positive development for hospital pharmacy.

    PubMed

    Lee, H E

    1983-06-01

    The development of premixed intravenous admixtures is reviewed in a historical context, and its effects on hospital pharmacy practice are discussed. As pharmaceutical manufacturers introduce more i.v. medications in ready-to-use containers, the same complaints that were voiced by pharmacists about unit dose packaging and ready-to-dispense tablets and capsules are being aired. But premixed i.v. admixtures are a logical extension of the basic unit dose principle of providing a readily identifiable and ready-to-administer dose. The time and cost savings these products offer are needed in hospital pharmacies. Some of the disadvantages of these products--including storage and freezer space and multiplicity of administration systems--are overcome by proper planning and education of personnel. If fewer personnel are now needed to prepare i.v. admixtures, then those personnel should be used to improve patient care in other ways. The use of premixed i.v. admixtures is a positive technological advance in drug packaging. Its advantages outweight its disadvantages, and it will soon be become the universally accepted form of i.v. drug packaging.

  11. Active Control for Statistically Stationary Turbulent PremixedFlame Simulations

    SciTech Connect

    Bell, J.B.; Day, M.S.; Grcar, J.F.; Lijewski, M.J.

    2005-08-30

    The speed of propagation of a premixed turbulent flame correlates with the intensity of the turbulence encountered by the flame. One consequence of this property is that premixed flames in both laboratory experiments and practical combustors require some type of stabilization mechanism to prevent blow-off and flashback. The stabilization devices often introduce a level of geometric complexity that is prohibitive for detailed computational studies of turbulent flame dynamics. Furthermore, the stabilization introduces additional fluid mechanical complexity into the overall combustion process that can complicate the analysis of fundamental flame properties. To circumvent these difficulties we introduce a feedback control algorithm that allows us to computationally stabilize a turbulent premixed flame in a simple geometric configuration. For the simulations, we specify turbulent inflow conditions and dynamically adjust the integrated fueling rate to control the mean location of the flame in the domain. We outline the numerical procedure, and illustrate the behavior of the control algorithm on methane flames at various equivalence ratios in two dimensions. The simulation data are used to study the local variation in the speed of propagation due to flame surface curvature.

  12. Large Eddy Simulation of High-Speed, Premixed Ethylene Combustion

    NASA Technical Reports Server (NTRS)

    Ramesh, Kiran; Edwards, Jack R.; Chelliah, Harsha; Goyne, Christopher; McDaniel, James; Rockwell, Robert; Kirik, Justin; Cutler, Andrew; Danehy, Paul

    2015-01-01

    A large-eddy simulation / Reynolds-averaged Navier-Stokes (LES/RANS) methodology is used to simulate premixed ethylene-air combustion in a model scramjet designed for dual mode operation and equipped with a cavity for flameholding. A 22-species reduced mechanism for ethylene-air combustion is employed, and the calculations are performed on a mesh containing 93 million cells. Fuel plumes injected at the isolator entrance are processed by the isolator shock train, yielding a premixed fuel-air mixture at an equivalence ratio of 0.42 at the cavity entrance plane. A premixed flame is anchored within the cavity and propagates toward the opposite wall. Near complete combustion of ethylene is obtained. The combustor is highly dynamic, exhibiting a large-scale oscillation in global heat release and mass flow rate with a period of about 2.8 ms. Maximum heat release occurs when the flame front reaches its most downstream extent, as the flame surface area is larger. Minimum heat release is associated with flame propagation toward the cavity and occurs through a reduction in core flow velocity that is correlated with an upstream movement of the shock train. Reasonable agreement between simulation results and available wall pressure, particle image velocimetry, and OH-PLIF data is obtained, but it is not yet clear whether the system-level oscillations seen in the calculations are actually present in the experiment.

  13. Cell factories for insulin production.

    PubMed

    Baeshen, Nabih A; Baeshen, Mohammed N; Sheikh, Abdullah; Bora, Roop S; Ahmed, Mohamed Morsi M; Ramadan, Hassan A I; Saini, Kulvinder Singh; Redwan, Elrashdy M

    2014-10-02

    The rapid increase in the number of diabetic patients globally and exploration of alternate insulin delivery methods such as inhalation or oral route that rely on higher doses, is bound to escalate the demand for recombinant insulin in near future. Current manufacturing technologies would be unable to meet the growing demand of affordable insulin due to limitation in production capacity and high production cost. Manufacturing of therapeutic recombinant proteins require an appropriate host organism with efficient machinery for posttranslational modifications and protein refolding. Recombinant human insulin has been produced predominantly using E. coli and Saccharomyces cerevisiae for therapeutic use in human. We would focus in this review, on various approaches that can be exploited to increase the production of a biologically active insulin and its analogues in E. coli and yeast. Transgenic plants are also very attractive expression system, which can be exploited to produce insulin in large quantities for therapeutic use in human. Plant-based expression system hold tremendous potential for high-capacity production of insulin in very cost-effective manner. Very high level of expression of biologically active proinsulin in seeds or leaves with long-term stability, offers a low-cost technology for both injectable as well as oral delivery of proinsulin.

  14. How insulin engages its primary binding site on the insulin receptor

    PubMed Central

    Menting, John G.; Whittaker, Jonathan; Margetts, Mai B.; Whittaker, Linda J.; Kong, Geoffrey K.-W.; Smith, Brian J.; Watson, Christopher J.; Žáková, Lenka; Kletvíková, Emília; Jiráček, Jiří; Chan, Shu Jin; Steiner, Donald F.; Dodson, Guy G.; Brzozowski, Andrzej M.; Weiss, Michael A.; Ward, Colin W.; Lawrence, Michael C.

    2013-01-01

    Insulin receptor signalling has a central role in mammalian biology, regulating cellular metabolism, growth, division, differentiation and survival1,2. Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus and the onset of Alzheimer’s disease3; aberrant signalling occurs in diverse cancers, exacerbated by crosstalk with the homologous type 1 insulin-like growth factor receptor (IGF1R)4. Despite more than three decades of investigation, the three-dimensional structure of the insulin–insulin receptor complex has proved elusive, confounded by the complexity of producing the receptor protein. Here we present the first view, to our knowledge, of the interaction of insulin with its primary binding site on the insulin receptor, on the basis of four crystal structures of insulin bound to truncated insulin receptor constructs. The direct interaction of insulin with the first leucine-rich-repeat domain (L1) of insulin receptor is seen to be sparse, the hormone instead engaging the insulin receptor carboxy-terminal α-chain (αCT) segment, which is itself remodelled on the face of L1 upon insulin binding. Contact between insulin and L1 is restricted to insulin B-chain residues. The αCT segment displaces the B-chain C-terminal β-strand away from the hormone core, revealing the mechanism of a long-proposed conformational switch in insulin upon receptor engagement. This mode of hormone–receptor recognition is novel within the broader family of receptor tyrosine kinases5. We support these findings by photo-crosslinking data that place the suggested interactions into the context of the holoreceptor and by isothermal titration calorimetry data that dissect the hormone–insulin receptor interface. Together, our findings provide an explanation for a wealth of biochemical data from the insulin receptor and IGF1R systems relevant to the design of therapeutic insulin analogues. PMID:23302862

  15. Analgesic efficacy of equimolar 50% nitrous oxide/oxygen gas premix (Kalinox®) as compared with a 5% eutectic mixture of lidocaine/prilocaine (EMLA®) in chronic leg ulcer debridement.

    PubMed

    Traber, Juerg; Held, Ulrike; Signer, Maria; Huebner, Tobias; Arndt, Stefan; Neff, Thomas A

    2016-08-08

    Chronic foot and leg ulcers are a common health problem worldwide. A mainstay of chronic ulcer therapy is sharp mechanical wound debridement requiring potent analgesia. In this prospective, controlled, single-centre, crossover design study, patients were assigned to either the administration of topical analgesia with 5% lidocaine/prilocaine cream or the inhalation of an analgesic 50% N2 O/O2 gas premix. Primary outcome parameter was level of pain at maximum wound depth during debridement as measured by a visual analogue scale. Secondary outcomes included level of pain after debridement, overall duration of treatment session, duration and completeness of debridement, and the patient's subjective perception of analgesic quality during debridement. Pain level increased from 0·60/0·94 (first/second debridement; baseline) to 1·76/2·50 (debridement) with 5% lidocaine/prilocaine and from 1·00/1·35 (baseline) to 3·95/3·29 (debridement) with 50% N2 O/O2 gas premix. Patient satisfaction was 90·48%/94·44% (first/second debridement) with topical 5% lidocaine/prilocaine analgesia and 90·48%/76·47% with the inhalation of 50% N2 O/O2 gas premix. Debridement was completed in a significantly higher percentage of 85·71%/88·89% (first/second debridement) with 5% lidocaine/prilocaine than with 50% N2 O/O2 gas premix (42·86%/58·82%) (odds ratio 6·7; P = 0·001). This study provides sound evidence that analgesia with topically administered 5% lidocaine/prilocaine cream is superior to the use of inhaled 50% N2 O/O2 gas premix in chronic leg ulcer debridement.

  16. Influence of Unweighting on Insulin Signal Transduction in Muscle

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.

    2002-01-01

    Unweighting of the juvenile soleus muscle is characterized by an increased binding capacity for insulin relative to muscle mass due to sparing of the receptors during atrophy. Although carbohydrate metabolism and protein degradation in the unweighted muscle develop increased sensitivity to insulin in vivo, protein synthesis in vivo and system A amino acid transport in vitro do not appear to develop such an enhanced response. The long-term goal is to identify the precise nature of this apparent resistance in the insulin signal transduction pathway and to consider how reduced weight-bearing may elicit this effect, by evaluating specific components of the insulin signalling pathway. Because the insulin-signalling pathway has components in common with the signal transduction pathway for insulin-like growth factor (IGF-1) and potentially other growth factors, the study could have important implications in the role of weight-bearing function on muscle growth and development. Since the insulin signalling pathway diverges following activation of insulin receptor tyrosine kinase, the immediate specific aims will be to study the receptor tyrosine kinase (IRTK) and those branches, which lead to phosphorylation of insulin receptor substrate-1 (IRS-1) and of Shc protein. To achieve these broader objectives, we will test in situ, by intramuscular injection, the responses of glucose transport, system A amino acid transport and protein synthesis to insulin analogues for which the receptor has either a weaker or much stronger binding affinity compared to insulin. Studies will include: (1) estimation of the ED(sub 50) for each analogue for these three processes; (2) the effect of duration (one to four days) of unweighting on the response of each process to all analogues tested; (3) the effect of unweighting and the analogues on IRTK activity; and (4) the comparative effects of unweighting and analogue binding on the tyrosine phosphorylation of IRTK, IRS-1, and Shc protein.

  17. Changes in insulin therapy regimens over 10 yr in children and adolescents with type 1 diabetes attending diabetes camps.

    PubMed

    Redon, Isabelle; Beltrand, Jacques; Martin, Delphine; Taupin, Pierre; Choleau, Carine; Morandini, Mélina; Cahané, Michel; Robert, Jean-Jacques

    2014-08-01

    To describe the changes in insulin therapy regimens of children and adolescents with type 1 diabetes over 10 yr and their correlation with hemoglobin A1c (HbA1c). The study included 7206 children and adolescents (age 12.8 ± 2.7 yr, more than 1 yr of diabetes duration) admitted in summer camps between 1998 and 2007 (707-896/yr). Based on injection times (breakfast, lunch, afternoon, dinner, bedtime) and insulin types (short, long and premixed; human or analog), 786 different therapeutic combinations were classified in six main types of regimens. The distribution of the different regimens and their correlation with HbA1c were evaluated as a function of year and age. Over 10 yr, basal bolus increased from 13 to 52% and the pump from <1 to 13%, regimens with two to three injections per day decreased from 50 to 25%, those with only premixed insulins from 33 to 7%, and diverse regimens from 9 to 1%. HbA1c was significantly higher with premixed insulin only, but there were no differences between the other regimens throughout the follow-up. Mean yearly HbA1c (8.21-8.45%) did not show any significant decrease, but the percentage of patients with HbA1c > 9 and 10% decreased significantly, in those treated with two to three injections and the pump, not with basal bolus or premixed only regimens. A major trend in intensifying insulin treatment in children and adolescents with type 1 diabetes was accompanied by modest improvements in HbA1c. No insulin regimen has shown any better results, except over premixed insulins. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Improvement in morning hyperglycaemia with basal human ultratard and prandial human actrapid insulin--a comparison of multiple injection regimens.

    PubMed

    Davies, R R; McEwen, J; Moreland, T A; Durnin, C; Newton, R W

    1988-10-01

    Three 'pen'-administered multiple injection regimens have been compared with twice daily insulin injection regimens by means of 24-h profiles of plasma glucose and free insulin concentrations. Ten Type 1 diabetic patients received their usual twice daily insulin regimen and were then randomized to receive the same total daily insulin dose in four divided doses using (1) 50:50 premixed soluble and isophane, (2) 30:70 premixed soluble and isophane, and (3) preprandial soluble and evening crystalline-zinc insulins. Profiles were performed after 1 week on each regimen. Plasma glucose concentrations were similar during the twice daily regimen and the two premixed regimens, rising during the early hours of the morning to a peak between 0900 and 0930 h of 13.8 +/- 2.8 (+/- SD) mmol l-1 on the twice daily regimen, 13.6 +/- 5.3 mmol l-1 on the premixed 50:50 regimen, and 13.5 +/- 4.2 mmol-1 on the premixed 30:70 regimen. With the basal and prandial regimen, overnight plasma glucose concentrations were higher than with the other regimens between 2400 and 0300 h (p less than 0.05). Concentrations then fell until breakfast, and rose after this meal to a peak of 9.5 +/- 4.3 mmol l-1 (p less than 0.01). Mean plasma glucose concentrations were significantly lower than on the other three regimens between 0830 and 1100 h (p less than 0.05). Less variability was observed in 24-h mean plasma glucose concentrations during the basal and prandial regimen than during the other three regimens.

  19. Premixed calcium phosphate cements: Synthesis, physical properties, and cell cytotoxicity

    PubMed Central

    Xu, Hockin H.K.; Carey, Lisa E.; Simon, Carl G.; Takagi, Shozo; Chow, Laurence C.

    2009-01-01

    Objectives Calcium phosphate cement (CPC) is a promising material for dental, periodontal, and craniofacial repairs. However, its use requires on-site powder–liquid mixing that increases the surgical placement time and raises concerns of insufficient and inhomogeneous mixing. The objective of this study was to determine a formulation of premixed CPC (PCPC) with rapid setting, high strength, and good in vitro cell viability. Methods PCPCs were formulated from CPC powder + non-aqueous liquid + gelling agent + hardening accelerator. Five PCPCs were thus developed: PCPC-Tartaric, PCPC-Malonic, PCPC-Citric, PCPC-Glycolic, and PCPC-Malic. Formulations and controls were compared for setting time, diametral tensile strength, and osteoblast cell compatibility. Results Setting time (mean ± S.D.; n = 4) for PCPC-Tartaric was 8.2 ± 0.8 min, significantly less than the 61.7 ± 1.5 min for the Premixed Control developed previously (p < 0.001). On 7th day immersion, the diametral tensile strength of PCPC-Tartaric reached 6.5 ± 0.8 MPa, higher than 4.5 ± 0.8 MPa of Premixed Control (p = 0.036). Osteoblast cells displayed a polygonal morphology and attached to the nano-hydroxyapatite crystals in the PCPCs. All cements had similar live cell density values (p = 0.126), indicating that the new PCPCs were as cell compatible as a non-premixed CPC control known to be biocompatible. Each of the new PCPCs had a cell viability that was not significantly different (p > 0.1) from that of the non-premixed CPC control. Significance PCPCs will eliminate the powder–liquid mixing during surgery and may also improve the cement performance. The new PCPCs supported cell attachment and yielded a high cell density and viability. Their mechanical strengths approached the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. These nano-crystalline hydroxyapatite cements may be useful in dental, periodontal, and craniofacial repairs. PMID:16678895

  20. Low pressure sooting flames : a way to laboratory analogues of various carbonaceous dust?

    NASA Astrophysics Data System (ADS)

    Cao, A. T.; Pino, T.; Carpentier, Y.; Dartois, E.; Vasquez, R.; Bréchignac, Ph.; D'Hendecourt, L.

    2007-12-01

    Our goal is the production of analogues of solid carbonaceous materials observed in many and various astrophysical environments. This should allow an exploration of their properties that requires larger amount of available materials and in particular the exploration of their evolution under various processes such as irradiation. The chemical reactor that is chosen is a low pressure sooting premixed flame, a model system for the combustion community. This reactor produces a large variety of soot under controlled conditions, ranging from hydrogenated amorphous carbon to strongly aromatic material. Their infrared spectroscopic studies will be presented and their pertinence to the study of extraterrestrial matter shown.

  1. Effect of combined application insulin and insulin detemir on continous glucose monitor in children with type 1 diabetes mellitus

    PubMed Central

    Chen, Xiao-Yun; Dong, Qing; Li, Gui-Mei

    2015-01-01

    Insulin detemir is a soluble long-acting human insulin analogue at neutral pH with a unique mechanism of action, which could strengthen the effects of insulin. This study aims to explore the effects of insulin combined with insulin detemir on the continous glucose in children with type 1 diabetes mellitus. In this study, 150 patients with type 1 diabetes enrolled were included and randomly divided into 3 groups: insulin group (group A), insulin detemir group (group B) and insulin combined with insulin detemir group (group C). Each subject underwent 72 h of continuous glucose monitoring (CGM). MAGE, HbA1c and Noctumal Hypoglycemia levels were examined by using the ELISA kits. The body weight changes were also detected in this study. The results indicated that the information including age, body weight, disease duration and glucose level and HbA1c percentage on the start time point among three groups indicated no statistical differences. Insulin combined with insulin detemir decrease MAGE and HbA1c level in Group C compared to Group A and Group A (P < 0.05). Insulin combined with insulin detemir decreas noctumal hypoglycemia levels and body weight changes (P < 0.05). In conclusion, this study confirmed efficacy of insulin detemir by demonstrating non-inferiority of insulin detemir compared with insulin with respect to HbA1c, with an improved safety profile including significantly fewer hypoglycaemic episodes and less undesirable weight gain in children. PMID:26064343

  2. Insulin allergy.

    PubMed

    Ghazavi, Mohammad K; Johnston, Graham A

    2011-01-01

    Insulin reactions occur rarely but are of tremendous clinical importance. The first was reported in 1922 as a callus reaction at the injection site of insufficiently purified bovine insulin. Porcine insulin was subsequently found to be less allergenic than bovine insulin. Increasingly pure insulins have decreased the risk of adverse reactions, and the production of recombinant insulin with the same amino sequence as human insulin saw a large decrease in adverse reactions. Currently, the prevalence of allergic reactions to insulin products appears to be approximately 2%, and less than one-third of these events have been considered related to the insulin itself. Other reactions occur due to the preservatives added to insulin, including zinc, protamine, and meta-cresol. Allergic reactions can be type I or immunoglobulin E-mediated, type III or Arthus, and type IV or delayed-type hypersensitivity reactions. Type I reactions are the most common and can, rarely, cause anaphylaxis. In contrast, type IV reactions can occur after a delay of several days. Investigations include skin prick testing, patch testing, intradermal testing, and occasionally, skin biopsy.

  3. Biosimilar insulins.

    PubMed

    Heinemann, Lutz

    2012-08-01

    Until now most insulin used in developed countries is manufactured and distributed by a small number of multinational companies. Other pharmaceutical companies - many of these are located in countries such as India or China - are also able to manufacture insulin with modern biotechnological methods. Additionally, the patents for many insulin formulations have expired or are going to expire soon. This enables such companies to produce insulins and to apply for market approval of these as biosimilar insulins (BIs) in highly regulated markets such as the EU or the US. To understand the complexity of BIs' approval and usage, scientific and regulatory aspects have to be discussed. Differences in the manufacturing process (none of the insulin-manufacturing procedures are identical) result in the fact that all insulin that might become BIs differ from the originator insulin to some extent. The question is, have such differences in the structure of the insulin molecule and or the purity and so on clinically relevant consequences for the biological effects induced or not. The guidelines already in place in the EU for market approval require that the manufacturer demonstrates that his insulin has a safety and efficacy profile that is similar to that of the 'original' insulin formulation. Recently guidelines for biosimilars were issued in the US; however, these do not cover insulin. Although a challenging approval process for insulins to become BI might be regarded as a hurdle to keep companies out of certain markets, it is fair to say that the potential safety and efficacy issues surrounding BI are substantial and relevant, and do warrant a careful and evidence-driven approval process. Nevertheless, it is very likely that in the next years, BIs will come to the market also in highly regulated markets.

  4. Dry low NOx combustion system with pre-mixed direct-injection secondary fuel nozzle

    DOEpatents

    Zuo, Baifang; Johnson, Thomas; Ziminsky, Willy; Khan, Abdul

    2013-12-17

    A combustion system includes a first combustion chamber and a second combustion chamber. The second combustion chamber is positioned downstream of the first combustion chamber. The combustion system also includes a pre-mixed, direct-injection secondary fuel nozzle. The pre-mixed, direct-injection secondary fuel nozzle extends through the first combustion chamber into the second combustion chamber.

  5. Insulin during pregnancy, labour and delivery.

    PubMed

    de Valk, Harold W; Visser, Gerard H A

    2011-02-01

    Optimal glycaemic control is of the utmost importance to achieve the best possible outcome of a pregnancy complicated by diabetes. This holds for pregnancies in women with preconceptional type 1 or type 2 diabetes as well as for pregnancies complicated by gestational diabetes. Glycaemic control is conventionally expressed in the HbA1c value but the HbA1c value does not completely capture the complexity of glycaemic control. The daily glucose profile measured by the patients themselves through measurements performed in capillary blood obtained by finger stick provides valuable information needed to adjust insulin therapy. Hypoglycaemia is the major threat to the pregnant woman or the woman with tight glycaemic control in the run-up to pregnancy. Repetitive hypoglycaemia can lead to hypoglycaemia unawareness, which is reversible with prevention of hypoglycaemia. A delicate balance should be struck between preventing hyperglycaemia and hypoglycaemia. Insulin requirements are not uniform across the day: it is low during the night with a more or less pronounced rise at dawn, followed by a gradual decrease during the remainder of the day. A basal amount of insulin is needed to regulate the endogenous glucose production, short-acting insulin shots are needed to handle exogenous glucose loads. Insulin therapy means two choices: the type of insulin used and the method of insulin administration. Regarding the type of insulin, the choice is between human and analogue insulins. The analogue short-acting insulin aspart has been shown to be safe during pregnancy in a randomised trial and has received registration for this indication; the short-acting analogue insulin lispro has been shown to be safe in observational studies. No such information is available on the long-acting insulin analogues detemir and glargine and both are prescribed off-label with human long-acting insulin as obvious alternatives. Randomised trials have not been able to show superiority of continuous

  6. [New insulin types in type 1 diabetes mellitus].

    PubMed

    Mesa, Jordi

    2015-07-20

    Since its discovery almost a century ago, insulin remains the mainstay of treatment of patients with type 1 diabetes mellitus. Although progress in the synthesis of new formulations has been remarkable, the physiological profile of insulin is still different from that observed with preparations available nowadays. In the last decade, the introduction into clinical practice of insulin analogues has allowed significantly improvement in glycemic control and has facilitated the spread of basal/bolus patterns, the most physiological ones until now. Despite the benefits of basal analogues, glycemia often varies considerably when used as a single daily injection and this is why new molecules have been further investigated. Improvement has been achieved especially in terms of duration and rate of hypoglycemia, the main limiting factor of intensive therapy. This article reviews the available data concerning the new basal insulin analogues, degludec, pegylated lispro and glargine U300, and new formulations currently under development.

  7. RANS/PDF and LES/FDF for prediction of turbulent premixed flames

    NASA Astrophysics Data System (ADS)

    Yilmaz, Server Levent

    Probability density function (PDF) and filtered density function (FDF) methodologies are developed and implemented, respectively, for Reynolds-averaged Navier-Stokes (RANS) and large eddy simulation (LES) of turbulent premixed flames. RANS predictions are made of a lean premixed bluff-body flame via the joint velocity-scalar-frequency PDF model. LES of a premixed Bunsen-burner flame is conducted via the scalar FDF methodology. Both simulations employ finite rate kinetics via a reduced methane chemistry mechanism to account for combustion. Prediction results are compared with experimental data, and are shown to capture some of the intricate physics of turbulent premixed combustion. Keywords. large eddy simulation, filtered density function, Reynolds-averaged Navier-Stokes, probability density function, turbulent reacting flows, lean premixed combustion.

  8. Importance of insulin immunoassays in the diagnosis of factitious hypoglycemia.

    PubMed

    Nalbantoğlu Elmas, Özlem; Demir, Korcan; Soylu, Nusret; Çelik, Nilüfer; Özkan, Behzat

    2014-12-01

    We report two cases emphasizing the importance of insulin assays for evaluation of hypoglycemia in diabetic patients. Case 1 was a 96/12-year-old female patient with type 1 diabetes mellitus and case 2 was a 1010/12-year-old male patient with DIDMOAD. Both patients were on a basal-bolus insulin regimen. Both were admitted because of persistent hypoglycemia. Analyses of serum samples obtained at the time of hypoglycemia initially showed low insulin and C-peptide levels. Recurrent episodes of unexplained hypoglycemia necessitated measurement of insulin levels by using different insulin assays, which revealed hyperinsulinemic hypoglycemia with low C-peptide levels, findings which confirmed a diagnosis of factitious hypoglycemia. Surreptitious administration of insulin should not be excluded in diabetic patients with hypoglycemia without taking into account the rate of cross-reactivity of insulin analogues with the insulin assay used.

  9. Combustion mechanism of ultralean rotating counterflow twin premixed flame

    NASA Astrophysics Data System (ADS)

    Uemichi, Akane; Nishioka, Makihito

    2015-01-01

    In our previous numerical studies [Nishioka Makihito, Zhenyu Shen, and Akane Uemichi. "Ultra-lean combustion through the backflow of burned gas in rotating counterflow twin premixed flames." Combustion and Flame 158.11 (2011): 2188-2198. Uemichi Akane, and Makihito Nishioka. "Numerical study on ultra-lean rotating counterflow twin premixed flame of hydrogen-air." Proceedings of the Combustion Institute 34.1 (2013): 1135-1142]. we found that methane- and hydrogen-air rotating counterflow twin flames (RCTF) can achieve ultralean combustion when backward flow of burned gas occurs due to the centrifugal force created by rotation. In this study, we investigated the mechanisms of ultralean combustion in these flames by the detailed numerical analyses of the convective and diffusive transport of the main species. We found that, under ultralean conditions, the diffusive transport of fuel exceeds its backward convective transport in the flame zone, which is located on the burned-gas side of the stagnation point. In contrast, the relative magnitudes of diffusive and convective transport for oxygen are reversed compared to those for the fuel. The resulting flows for fuel and oxygen lead to what we call a 'net flux imbalance'. This net flux imbalance increases the flame temperature and concentrations of active radicals. For hydrogen-air RCTF, a very large diffusivity of hydrogen enhances the net flux imbalance, significantly increasing the flame temperature. This behaviour is intrinsic to a very lean premixed flame in which the reaction zone is located in the backflow of its own burned gas.

  10. Measurements and large eddy simulation of propagating premixed flames

    SciTech Connect

    Masri, A.R.; Cadwallader, B.J.; Ibrahim, S.S.

    2006-07-15

    This paper presents an experimental and numerical study of unsteady turbulent premixed flames igniting in an initially stagnant mixture and propagating past solid obstacles. The objective here is to study the outstanding issue of flow-flame interactions in transient premixed combustion environments. Particular emphasis is placed on the burning rate and the structure of the flame front. The experimental configuration consists of a chamber with a square cross-section filled with a combustible mixture of propane-air ignited from rest. An array of baffle plates as well as geometrical obstructions of varying shapes and blockage ratios, are placed in the path of the flame as it propagates from the ignition source to the vented end of the enclosure. A range of flame propagation conditions are studied experimentally. Measurements are presented for pressure-time traces, high-speed images of the flame front, mean velocities obtained from particle imaging velocimetry and laser induced fluorescence images of the hydroxyl radical OH. Three-dimensional large eddy simulations (LES) are also made for a case where a square obstacle and an array of baffle plates are placed in the chamber. The dynamic Germano model and a simple flamelet combustion model are used at the sub-grid scale. The effects of grid size and sub-grid filter width are also discussed. Calculations and measurements are found to be in good agreement with respect to flame structure and peak overpressure. Turbulence levels increase significantly at the leading edge of the flame as it propagates past the array of baffle plates and the obstacle. With reference to the regime diagrams for turbulent premixed combustion, it is noted that the flame continues to lie in the zones of thin reactions or corrugated flamelets regardless of the stage of propagation along the chamber. (author)

  11. Field Effects of Buoyancy on Lean Premixed Turbulent Flames

    NASA Technical Reports Server (NTRS)

    Cheng, R. K.; Johnson, M. R.; Greenberg, P. S.; Wernet, M. P.

    2003-01-01

    The study of field effects of buoyancy on premixed turbulent flames is directed towards the advancement of turbulent combustion theory and the development of cleaner combustion technologies. Turbulent combustion is considered the most important unsolved problem in combustion science and laboratory studies of turbulence flame processes are vital to theoretical development. Although buoyancy is dominant in laboratory flames, most combustion models are not yet capable to consider buoyancy effects. This inconsistency has impeded the validation of theories and numerical simulations with experiments. Conversely, the understanding of buoyancy effects is far too limited to help develop buoyant flame models. Our research is also relevant to combustion technology because lean premixed combustion is a proven method to reduce the formation of oxides of nitrogen (NOx). In industrial lean premixed combustion systems, their operating conditions make them susceptible to buoyancy thus affecting heat distribution, emissions, stability, flashback and blowoff. But little knowledge is available to guide combustion engineers as to how to avoid or overcome these problems. Our hypothesis is that through its influence on the mean pressure field, buoyancy has direct and indirect effects on local flame/turbulence interactions. Although buoyancy acts on the hot products in the farfield the effect is also felt in the nearfield region upstream of the flame. These changes also influence the generation and dissipation of turbulent kinetic energy inside the flame brush and throughout the flowfield. Moreover, the plume of an open flame is unstable and the periodic fluctuations make additional contributions to flame front dynamics in the farfield. Therefore, processes such as flame wrinkling, flow acceleration due to heat release and flame- generated vorticity are all affected. Other global flame properties (e.g. flame stabilization limits and flame speed) may all be coupled to buoyancy. This

  12. Periodic and Chaotic Modes in Premixed Laminar Flames

    NASA Astrophysics Data System (ADS)

    El-Hamdi, Mohamed Abbes

    1991-06-01

    In this thesis, we report the discoveries of many periodic and chaotic modes of laminar premixed flames on porous plug burners. This report is the first confirmation of predictions of a number of recent theoretical studies on the dynamics of premixed flames. The experimental innovations and techniques presented in section 3.6 are at the heart of the discoveries of these dynamical modes. In our experiments, a flame front is stabilized on a porous plug burner enclosed within a pyrex chamber. By varying the total flow rate, the stoichiometry of the combustible mixture, and the chamber pressure, we discovered many periodic and chaotic modes. We show that different fuels and/or oxidizers as well as the symmetries of the system can affect the dynamics of the flame front. Experimental evidence is presented that shows that laminar premixed flames exhibit low-dimensional, deterministic chaos. The largest Liapunov exponent and the pointwise dimension calculations are used to confirm that chaos exists in certain regions of parameter space. We also describe a power spectrum technique that can be used to identify deterministic dynamics in real time. With the help of a spectrum analyzer, an experimentalist can map the dynamics (simple and complex) of the system under investigation in a relatively short time. As far as we know, this is the first time that nonlinear dynamics techniques are used to analyze experimental data from combustion. All the nonperiodic modes that we have discovered exhibit low-dimensional deterministic chaos and we believe that this result is a general one for propagating fronts. The implication of our work is that such nonperiodic states can be described by a tractable set of ordinary differential equations.

  13. Jet flow and premixed jet flame control by plasma swirler

    NASA Astrophysics Data System (ADS)

    Li, Gang; Jiang, Xi; Zhao, Yujun; Liu, Cunxi; Chen, Qi; Xu, Gang; Liu, Fuqiang

    2017-04-01

    A swirler based on dielectric barrier discharge plasma actuators is designed and its effectiveness in both jet flow and premixed jet flame control is demonstrated. In contrast to traditional spanwise-oriented actuators, plasma actuators are placed along the axial direction of the injector to induce a circumferential velocity to the main flow and create a swirl flow without any insertion or moving part. In the DBD plasma swirl injector, the discharge does not ignite the mixture nor does it induce flashback. Flame visualization is obtained by cameras while velocity profiles are obtained by Laser Doppler Anemometry measurements. The results obtained indicate the effectiveness of the new design.

  14. Response mechanisms of attached premixed flames subjected to harmonic forcing

    NASA Astrophysics Data System (ADS)

    Shreekrishna

    The persistent thrust for a cleaner, greener environment has prompted air pollution regulations to be enforced with increased stringency by environmental protection bodies all over the world. This has prompted gas turbine manufacturers to move from nonpremixed combustion to lean, premixed combustion. These lean premixed combustors operate quite fuel-lean compared to the stochiometric, in order to minimize CO and NOx productions, and are very susceptible to oscillations in any of the upstream flow variables. These oscillations cause the heat release rate of the flame to oscillate, which can engage one or more acoustic modes of the combustor or gas turbine components, and under certain conditions, lead to limit cycle oscillations. This phenomenon, called thermoacoustic instabilities, is characterized by very high pressure oscillations and increased heat fluxes at system walls, and can cause significant problems in the routine operability of these combustors, not to mention the occasional hardware damages that could occur, all of which cumulatively cost several millions of dollars. In a bid towards understanding this flow-flame interaction, this research works studies the heat release response of premixed flames to oscillations in reactant equivalence ratio, reactant velocity and pressure, under conditions where the flame preheat zone is convectively compact to these disturbances, using the G-equation. The heat release response is quantified by means of the flame transfer function and together with combustor acoustics, forms a critical component of the analytical models that can predict combustor dynamics. To this end, low excitation amplitude (linear) and high excitation amplitude (nonlinear) responses of the flame are studied in this work. The linear heat release response of lean, premixed flames are seen to be dominated by responses to velocity and equivalence ratio fluctuations at low frequencies, and to pressure fluctuations at high frequencies which are in the

  15. Combustion Dynamics of Plasma-Enhanced Premixed and Nonpremixed Flames

    DTIC Science & Technology

    2010-12-01

    flame. The anchor of the nonpremixed flame can be seen at the base of the plasma plume. Both the size and luminosity of the plume increase as a...K higher than that in nonpremixed flames for the same fuel flow rates. For premixed flames, the visible flame luminosity and plasma volume increase...vol. 34, no. 6, pp. 2545–2551, Dec. 2006. [10] W. Kim, M. Godfrey Mungal, and M. A. Cappelli, “The role of in situ reforming in plasma enhanced ultra

  16. Premixer assembly for mixing air and fuel for combustion

    SciTech Connect

    York, William David; Johnson, Thomas Edward; Keener, Christopher Paul

    2016-12-13

    A premixer assembly for mixing air and fuel for combustion includes a plurality of tubes disposed at a head end of a combustor assembly. Also included is a tube of the plurality of tubes, the tube including an inlet end and an outlet end. Further included is at least one non-circular portion of the tube extending along a length of the tube, the at least one non-circular portion having a non-circular cross-section, and the tube having a substantially constant cross-sectional area along its length

  17. Proinsulin modified by analogues of arginine and lysine is degraded rapidly in pancreatic B-cells.

    PubMed Central

    Halban, P A; Amherdt, M; Orci, L; Renold, A E

    1984-01-01

    Modified cytosolic proteins are known to be degraded more rapidly than their native counterparts. In order to determine whether the same applies to a modified protein within the potentially protective environment of secretory granules, rat islets were labelled [( 3H]leucine) in the presence or absence (controls) of 3 mM-canavanine and 3 mM-thialysine (analogues of arginine and lysine respectively), followed by a 24h 'chase' period without analogues. The results showed the following. (1) Incorporation of the analogues into newly synthesized labelled proinsulin inhibited its conversion into insulin during the chase period. (2) Despite this block in conversion, the modified proinsulin was released from islets at the same rate as native proinsulin and insulin from control islets. (3) Morphometric analysis of high-resolution autoradiographs showed that products labelled in the presence of analogues were sequestered into secretory granules at the same rate as native products in control B-cells. (4) Only 7% of prelabelled proinsulin had been degraded within islet cells during the chase period in control islets, compared with 36% for proinsulin prelabelled in the presence of analogues. (5) Control experiments showed that the analogues had no effect on the release or intracellular degradation of unmodified stored insulin (present in islets before exposure to the analogues). (6) Despite sequestration into secretory granules, modified proinsulin, if not released from B-cells, is thus degraded more rapidly than native products. PMID:6372788

  18. Natural Analogue Synthesis Report

    SciTech Connect

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide

  19. Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator 3. Early Plasma Insulin Determinations

    PubMed Central

    Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

    2009-01-01

    Introduction AIDA is an interactive educational diabetes simulator that has been available without charge via the Internet for over 12 years. Recent articles have described the incorporation of a novel generic model of insulin absorption into AIDA as a way of enhancing its capabilities. The basic model components to be integrated have been overviewed, with the aim being to provide simulations of regimens utilizing insulin analogues, as well as insulin doses greater than 40 IU (the current upper limit within the latest release of AIDA [v4.3a]). Some preliminary calculated insulin absorption results have also recently been described. Methods This article presents the first simulated plasma insulin profiles from the integration of the generic subcutaneous insulin absorption model, and the currently implemented model in AIDA for insulin disposition. Insulin absorption has been described by the physiologically based model of Tarín and colleagues. A single compartment modeling approach has been used to specify how absorbed insulin is distributed in, and eliminated from, the human body. To enable a numerical solution of the absorption model, a spherical subcutaneous depot for the injected insulin dose has been assumed and spatially discretized into shell compartments with homogeneous concentrations, having as its center the injection site. The number of these compartments will depend on the dose and type of insulin. Insulin inflow arises as the sum of contributions to the different shells. For this report the first bench testing of plasma insulin determinations has been done. Results Simulated plasma insulin profiles are provided for currently available insulin preparations, including a rapidly acting insulin analogue (e.g., lispro/Humalog or aspart/Novolog), a short-acting (regular) insulin preparation (e.g., Actrapid), intermediate-acting insulins (both Semilente and neutral protamine Hagedorn types), and a very long-acting insulin analogue (e.g., glargine/Lantus), as

  20. FUEL INTERCHANGEABILITY FOR LEAN PREMIXED COMBUSTION IN GAS TURBINE ENGINES

    SciTech Connect

    Don Ferguson; Geo. A. Richard; Doug Straub

    2008-06-13

    In response to environmental concerns of NOx emissions, gas turbine manufacturers have developed engines that operate under lean, pre-mixed fuel and air conditions. While this has proven to reduce NOx emissions by lowering peak flame temperatures, it is not without its limitations as engines utilizing this technology are more susceptible to combustion dynamics. Although dependent on a number of mechanisms, changes in fuel composition can alter the dynamic response of a given combustion system. This is of particular interest as increases in demand of domestic natural gas have fueled efforts to utilize alternatives such as coal derived syngas, imported liquefied natural gas and hydrogen or hydrogen augmented fuels. However, prior to changing the fuel supply end-users need to understand how their system will respond. A variety of historical parameters have been utilized to determine fuel interchangeability such as Wobbe and Weaver Indices, however these parameters were never optimized for today’s engines operating under lean pre-mixed combustion. This paper provides a discussion of currently available parameters to describe fuel interchangeability. Through the analysis of the dynamic response of a lab-scale Rijke tube combustor operating on various fuel blends, it is shown that commonly used indices are inadequate for describing combustion specific phenomena.

  1. Evaluation of fuel preparation systems for lean premixing- prevaporizing combustors

    SciTech Connect

    Dodds, W.J.; Ekstedt, .E.E.

    1986-04-01

    A series of tests was conducted to provide data for the design of premixing-prevaporizing fuel-air mixture preparation systems for aircraft gas turbine engine combustors. Fifteen configurations of four different fuel-air mixture preparation system design concepts were evaluated to determine fuel-air mixture uniformity at the system exit over a range of conditions representative of cruise operation for a modern commercial turbofan engine. Operating conditions, including pressure, temperature, fuel-air ratio and velocity had no clear effect on mixture uniformity in systems which used low-pressure fuel injectors. However, performance of systems using pressure atomizing fuel nozzles and large-scale mixing devices was shown to be sensitive to operating conditions. Variations in system design variables were also evaluated and correlated. Mixture uniformity improved with increased system length, pressure drop, and number of fuel injection points per unit area. A premixing system compatible with the combustor envelope of a typical combustion system and capable of providing mixture nonuniformity (standard deviation/mean) below 15% over a typical range of cruise operating conditions was demonstrated.

  2. Experimental study of premixed flames in intense isotropic turbulence

    SciTech Connect

    Bedat, B.; Cheng, R.K.

    1994-04-01

    A methodology for investigating premixed turbulent flames propagating in intense isotropic turbulence has been developed. The burner uses a turbulence generator developed by Videto and Santavicca and the flame is stabilized by weak-swirl generated by air injectors. This set-up produces stable premixed turbulent flames under a wide range of mixture conditions and turbulence intensities. The experiments are designed to investigate systematically the changes in flame structures for conditions which can be classified as wrinkled laminar flames, corrugated flames and flames with distributed reaction zones. Laser Doppler anemometry and Rayleigh scattering techniques are used to determine the turbulence and scalar statistics. In the intense turbulence, the flames are found to produce very little changes in the mean and rams velocities. Their flame speed increase linearly with turbulence intensity as for wrinkled laminar flames. The Rayleigh scattering pdfs for flames within the distributed reaction zone regime are distinctly bimodal. The probabilities of the reacting states (i.e. contributions from within the reaction zone) is not higher than those of wrinkled laminar flame. These results show that there is no drastic changes in flame structures at Karlovitz number close to unity. This suggest that the Klimov-Williams criterion under-predicts the resilience of wrinkled flamelets to intense turbulence.

  3. Multiple mapping conditioning for flames with partial premixing

    SciTech Connect

    Kronenburg, A.; Cleary, M.J.

    2008-10-15

    Fully closed multiple mapping conditioning (MMC) is used to model partially premixed flames in homogeneous, isotropic decaying turbulence where the partial premixing is caused by local extinction and reignition phenomena. Two reference variables that represent mixing and reaction progress, such as mixture fraction and sensible enthalpy, are used to emulate turbulent scalar fluctuations. Local extinction is achieved by a priori coupling between scalar dissipation and temperature fluctuations via a correlation function that is based on the conditionally averaged sensible enthalpy at stoichiometric composition. The proposed model provides closures for the joint PDF of mixture fraction and sensible enthalpy, for the conditional variance equation of a reactive scalar, and for the doubly conditioned dissipation terms. Model results are compared with DNS in three flame cases with varying levels of local extinction, up to global extinction. The joint PDF predicted by MMC is in fair agreement with DNS. It constitutes, however, a clear improvement over conventional models using preassumed distribution functions for the PDFs. The doubly conditioned dissipation terms are modeled well and the results for all major chemical species are in good agreement with DNS. Predictions for intermediate species are also satisfactory. (author)

  4. Finite amplitude wave interaction with premixed laminar flames

    NASA Astrophysics Data System (ADS)

    Aslani, Mohamad; Regele, Jonathan D.

    2014-11-01

    The physics underlying combustion instability is an active area of research because of its detrimental impact in many combustion devices, such as turbines, jet engines, and liquid rocket engines. Pressure waves, ranging from acoustic waves to strong shocks, are potential sources of these disturbances. Literature on flame-disturbance interactions are primarily focused on either acoustics or strong shock wave interactions, with little information about the wide spectrum of behaviors that may exist between these two extremes. For example, the interaction between a flame and a finite amplitude compression wave is not well characterized. This phenomenon is difficult to study numerically due to the wide range of scales that need to be captured, requiring powerful and efficient numerical techniques. In this work, the interaction of a perturbed laminar premixed flame with a finite amplitude compression wave is investigated using the Parallel Adaptive Wavelet Collocation Method (PAWCM). This method optimally solves the fully compressible Navier-Stokes equations while capturing the essential scales. The results show that depending on the amplitude and duration of a finite amplitude disturbance, the interaction between these waves and premixed flames can produce a broad range of responses.

  5. Establishing bioequivalence of veterinary premixes (Type A medicated articles).

    PubMed

    Hunter, R P; Lees, P; Concordet, D; Toutain, P-L

    2012-04-01

    a) Key issues concerning Premix (Type A medicated articles) Bioequivalence evaluations: 1) This is a complex issue concerning both route of administration and formulation. 2) If the animal is not at the bunk/trough, the animal is not self-administering (eating medicated feed), thus there can be no drug absorption. b) Differing opinions among scientists and regulatory authorities/expert bodies regarding: 1) No harmonization on how to design, conduct, and interpret in vivo studies. 2) Applicability of biowaivers to Type A (premix) products. 3) Why are topdress and complete feed considered differently? Are they different formulations or different routes of administration? 4) Single dose vs. multi-dose studies. 5) What is the final formulation? c) What are the next steps: 1) Harmonize current bioequivalence guidelines through the VICH process. 2) Determine the applicability/non-applicability of the Biopharmaceutical Classification System (BCS). 3) Establish the Total Mixed Ration (i.e. formulation) effects. 4) Define the test subject (individual, pen, etc.). © 2012 Blackwell Publishing Ltd.

  6. Streamline segment statistics of premixed flames with nonunity Lewis numbers

    NASA Astrophysics Data System (ADS)

    Chakraborty, Nilanjan; Wang, Lipo; Klein, Markus

    2014-03-01

    The interaction of flame and surrounding fluid motion is of central importance in the fundamental understanding of turbulent combustion. It is demonstrated here that this interaction can be represented using streamline segment analysis, which was previously applied in nonreactive turbulence. The present work focuses on the effects of the global Lewis number (Le) on streamline segment statistics in premixed flames in the thin-reaction-zones regime. A direct numerical simulation database of freely propagating thin-reaction-zones regime flames with Le ranging from 0.34 to 1.2 is used to demonstrate that Le has significant influences on the characteristic features of the streamline segment, such as the curve length, the difference in the velocity magnitude at two extremal points, and their correlations with the local flame curvature. The strengthenings of the dilatation rate, flame normal acceleration, and flame-generated turbulence with decreasing Le are principally responsible for these observed effects. An expression for the probability density function (pdf) of the streamline segment length, originally developed for nonreacting turbulent flows, captures the qualitative behavior for turbulent premixed flames in the thin-reaction-zones regime for a wide range of Le values. The joint pdfs between the streamline length and the difference in the velocity magnitude at two extremal points for both unweighted and density-weighted velocity vectors are analyzed and compared. Detailed explanations are provided for the observed differences in the topological behaviors of the streamline segment in response to the global Le.

  7. Mass discrimination effects in MBMS study of rich premixed flames

    SciTech Connect

    Vovelle, C.; Doute, C.; Delfau, J.L.

    1995-03-01

    Sampling by formation of a molecular beam in mixtures containing both light and heavy species can be affected by mass discrimination effects. This situation is faced in rich premixed flames where H{sub 2} and H atoms are present in high concentration in mixture with heavier combustion products. This paper describes the results of a specific study carried out to derive a procedure that takes into account these effects and improves the accuracy of H{sub 2} and H measurements in flames. A three stage Molecular Beam Mass Spectrometer (MBMS) apparatus especially designed for the experimental determination of the structure of low pressure premixed flames has been used to study the effect of temperature (T) and mean molar mass (M) on the signals measured for species in mixtures of known composition. Variations of T and M where aimed at reproducing the evolution observed in flames when the sampling probe is moved from unburned, (low T, high M) to burned gases (high T, low M). However, as temperature variations were limited to the range 300-800K, the pressure was also varied from 13 down to 0.8 kPa to create sample density conditions equivalent to those prevailing in post flame gases. Most measurements have been performed with H{sub 2}/CH{sub 4}/N{sub 2}/O{sub 2}/Ar/CO{sub 2} mixtures while variations of the mean molar mass were achieved with binary H{sub 2}/Ar mixtures.

  8. Temperature response of turbulent premixed flames to inlet velocity oscillations

    NASA Astrophysics Data System (ADS)

    Ayoola, B.; Hartung, G.; Armitage, C. A.; Hult, J.; Cant, R. S.; Kaminski, C. F.

    2009-01-01

    Flame-turbulence interactions are at the heart of modern combustion research as they have a major influence on efficiency, stability of operation and pollutant emissions. The problem remains a formidable challenge, and predictive modelling and the implementation of active control measures both rely on further fundamental measurements. Model burners with simple geometry offer an opportunity for the isolation and detailed study of phenomena that take place in real-world combustors, in an environment conducive to the application of advanced laser diagnostic tools. Lean premixed combustion conditions are currently of greatest interest since these are able to provide low NO x and improved increased fuel economy, which in turn leads to lower CO2 emissions. This paper presents an experimental investigation of the response of a bluff-body-stabilised flame to periodic inlet fluctuations under lean premixed turbulent conditions. Inlet velocity fluctuations were imposed acoustically using loudspeakers. Spatially resolved heat release rate imaging measurements, using simultaneous planar laser-induced fluorescence (PLIF) of OH and CH2O, have been performed to explore the periodic heat release rate response to various acoustic forcing amplitudes and frequencies. For the first time we use this method to evaluate flame transfer functions and we compare these results with chemiluminescence measurements. Qualitative thermometry based on two-line OH PLIF was also used to compare the periodic temperature distribution around the flame with the periodic fluctuation of local heat release rate during acoustic forcing cycles.

  9. Vorticity isotropy in high Karlovitz number premixed flames

    NASA Astrophysics Data System (ADS)

    Bobbitt, Brock; Blanquart, Guillaume

    2016-10-01

    The isotropy of the smallest turbulent scales is investigated in premixed turbulent combustion by analyzing the vorticity vector in a series of high Karlovitz number premixed flame direct numerical simulations. It is found that increasing the Karlovitz number and the ratio of the integral length scale to the flame thickness both reduce the level of anisotropy. By analyzing the vorticity transport equation, it is determined that the vortex stretching term is primarily responsible for the development of any anisotropy. The local dynamics of the vortex stretching term and vorticity resemble that of homogeneous isotropic turbulence to a greater extent at higher Karlovitz numbers. This results in small scale isotropy at sufficiently high Karlovitz numbers and supports a fundamental similarity of the behavior of the smallest turbulent scales throughout the flame and in homogeneous isotropic turbulence. At lower Karlovitz numbers, the vortex stretching term and the vorticity alignment in the strain-rate tensor eigenframe are altered by the flame. The integral length scale has minimal impact on these local dynamics but promotes the effects of the flame to be equal in all directions. The resulting isotropy in vorticity does not reflect a fundamental similarity between the smallest turbulent scales in the flame and in homogeneous isotropic turbulence.

  10. Auto-ignition system for premixed gas turbine combustors

    SciTech Connect

    Mumford, S.E.

    1993-08-24

    In a gas turbine power plant having at least one combustor, the combustor is described comprising a pilot section and a main burn section, the pilot section, having a recirculation zone and comprising inlet air vents for providing inlet air into the recirculation zone, the main burn section being downstream and adjacent to the pilot section, a method for establishing a diffusion flame in the pilot section, comprising the steps of: injecting a flow of natural gas fuel into the pilot section; providing inlet air into the recirculation zone through the inlet air vents; operating the pilot section in a premix mode where the natural gas fuel mixes with the inlet air without combustion in the pilot section; and injecting a flow of liquid fuel into the recirculation zone of the pilot section just prior to the end of operation of the pilot section in the premix mode, the liquid fuel having an auto-ignition temperature less than the temperature of the inlet air, whereby the liquid fuel is auto-ignited in the recirculation zone and the natural gas fuel bursts into flame to establish the diffusion flame in the pilot section.

  11. Velocity and Reactive Scalar Dissipation Spectra in Turbulent Premixed Flames

    DOE PAGES

    Kolla, Hemanth; Zhao, Xin-Yu; Chen, Jacqueline H.; ...

    2016-06-09

    Dissipation spectra of velocity and reactive scalars—temperature and fuel mass fraction—in turbulent premixed flames are studied using direct numerical simulation data of a temporally evolving lean hydrogen-air premixed planar jet (PTJ) flame and a statistically stationary planar lean methane-air (SP) flame. Furthermore, the equivalence ratio in both cases was 0.7, the pressure 1 atm while the unburned temperature was 700 K for the hydrogen-air PTJ case and 300 K for methane-air SP case, that resulted in data sets with a density ratio of 3 and 5, respectively. The turbulent Reynolds numbers for the cases ranged from 200 to 428.4, themore » Damköhler number from 3.1 to 29.1, and the Karlovitz number from 0.1 to 4.5. The dissipation spectra collapse when normalized by the respective Favre-averaged dissipation rates. But, the normalized dissipation spectra in all the cases deviate noticeably from those predicted by classical scaling laws for constant-density turbulent flows and bear a clear influence of the chemical reactions on the dissipative range of the energy cascade.« less

  12. Velocity and Reactive Scalar Dissipation Spectra in Turbulent Premixed Flames

    SciTech Connect

    Kolla, Hemanth; Zhao, Xin-Yu; Chen, Jacqueline H.; Swaminathan, N.

    2016-06-09

    Dissipation spectra of velocity and reactive scalars—temperature and fuel mass fraction—in turbulent premixed flames are studied using direct numerical simulation data of a temporally evolving lean hydrogen-air premixed planar jet (PTJ) flame and a statistically stationary planar lean methane-air (SP) flame. Furthermore, the equivalence ratio in both cases was 0.7, the pressure 1 atm while the unburned temperature was 700 K for the hydrogen-air PTJ case and 300 K for methane-air SP case, that resulted in data sets with a density ratio of 3 and 5, respectively. The turbulent Reynolds numbers for the cases ranged from 200 to 428.4, the Damköhler number from 3.1 to 29.1, and the Karlovitz number from 0.1 to 4.5. The dissipation spectra collapse when normalized by the respective Favre-averaged dissipation rates. But, the normalized dissipation spectra in all the cases deviate noticeably from those predicted by classical scaling laws for constant-density turbulent flows and bear a clear influence of the chemical reactions on the dissipative range of the energy cascade.

  13. Mixing Model Performance in Non-Premixed Turbulent Combustion

    NASA Astrophysics Data System (ADS)

    Pope, Stephen B.; Ren, Zhuyin

    2002-11-01

    In order to shed light on their qualitative and quantitative performance, three different turbulent mixing models are studied in application to non-premixed turbulent combustion. In previous works, PDF model calculations with detailed kinetics have been shown to agree well with experimental data for non-premixed piloted jet flames. The calculations from two different groups using different descriptions of the chemistry and turbulent mixing are capable of producing the correct levels of local extinction and reignition. The success of these calculations raises several questions, since it is not clear that the mixing models used contain an adequate description of the processes involved. To address these questions, three mixing models (IEM, modified Curl and EMST) are applied to a partially-stirred reactor burning hydrogen in air. The parameters varied are the residence time and the mixing time scale. For small relative values of the mixing time scale (approaching the perfectly-stirred limit) the models yield the same extinction behavior. But for larger values, the behavior is distictly different, with EMST being must resistant to extinction.

  14. Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes.

    PubMed

    Colatrella, Antonietta; Visalli, Natalia; Abbruzzese, Santina; Leotta, Sergio; Bongiovanni, Marzia; Napoli, Angela

    2013-01-01

    Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c), hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P < 0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin) were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement.

  15. Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes

    PubMed Central

    Visalli, Natalia; Abbruzzese, Santina; Bongiovanni, Marzia; Napoli, Angela

    2013-01-01

    Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c), hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P < 0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin) were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement. PMID:23840206

  16. Influence of water content on hardening and handling of a premixed calcium phosphate cement.

    PubMed

    Engstrand, Johanna; Aberg, Jonas; Engqvist, Håkan

    2013-01-01

    Handling of calcium phosphate cements is difficult, where problems often arise during mixing, transferring to syringes, and subsequent injection. Via the use of premixed cements the risk of handling complications is reduced. However, for premixed cements to work in a clinical situation the setting time needs to be improved. The objective of this study is to investigate the influence of the addition of water on the properties of premixed cement. Monetite-forming premixed cements with small amounts of added water (less than 6.8 wt.%) were prepared and the influence on injectability, working time, setting time and mechanical strength was evaluated. The results showed that the addition of small amounts of water had significant influence on the properties of the premixed cement. With the addition of just 1.7 wt.% water, the force needed to extrude the cement from a syringe was reduced from 107 (±15) N to 39 (±9) N, the compression strength was almost doubled, and the setting time decreased from 29 (±4) min to 19 (±2) min, while the working time remained 5 to 6h. This study demonstrates the importance of controlling the water content in premixed cement pastes and how water can be used to improve the properties of premixed cements.

  17. Inpatient management of type 2 Diabetes Mellitus: Does choice of insulin regimen really matter?

    PubMed Central

    Akhtar, Syed Tehseen; Mahmood, Khalid; Naqvi, Iftikhar Haider; Vaswani, Aneel Sham

    2014-01-01

    Objective: To assess inpatient management of non-critically ill type 2 diabetics with different insulin regimen. Methods: We reviewed the medical records of all non-critically ill type 2 diabetic patients more than 18 years of age in medical department of civil hospital Karachi and Dow University of Health Sciences from January 2011 to December 2012. We collected the data from case records in data collection sheets that fulfill the inclusion criteria and divided the study subjects into three groups according to insulin regimen they received. Results: A total of 416 patients were analyzed out of which 220 were male. Subjects were divided into three groups according to insulin regimen they received. Majority were put on sliding scale of insulin (44.7%), while 33.1% and 22.1% subjects received basal bolus and pre-mixed insulin regimen respectively. Patients treated with basal bolus regimen had greater improvement in glycaemic control with short duration of hospital stay as compared to other two groups. The mean hyperglycaemic events were higher in sliding scale group while mean hypoglycaemic events were higher in basal bolus group. Conclusion: In non-critically ill type 2 diabetic patients the basal bolus regimen is superior to sliding and pre-mixed insulin regimen. Sliding scale should be discouraged in non-critically ill type 2 diabetic patients. PMID:25097540

  18. New ways of insulin delivery.

    PubMed

    Heinemann, L

    2011-02-01

    The predominant number of papers published from the middle of 2009 to the middle of 2010 about alternative routes of insulin administration (ARIA) were still about inhaled insulin. Long-term experience with Exubera was the topic of a number of publications that are also of relevance for inhaled insulin in general. The clinical trials performed with AIR insulin by Eli Lilly were published in a supplement issue of one diabetes technology journal and most of these will be presented. A number of other publications (also one in a high ranked journal) about their inhaled insulin were from another company: MannKind. The driving force behind Technosphere insulin (TI) - which is the only one still in clinical development - is Al Mann; he has put a lot of his personal fortune in this development. We will know the opinion of the regulatory authorities about TI in the near future; however, I am personally relatively confident that the Food and Drug Administration will provide TI with market approval. The more critical question for me is: will diabetologists and patients jump on this product once it becomes commercially available? Will it become a commercial success? In view of many negative feelings in the scientific community about inhaled insulin, it might be of help that MannKind publish their studies with TI systematically. Acknowledging being a believer in this route of insulin administration myself, one has to state that Exubera and AIR insulin had not offered profound advantages in terms of pharmacokinetic (PK) and pharmacodynamic (PD) properties in comparison with subcutaneously (SC) applied regular human insulin (RHI) and rapid-acting insulin analogues. The time-action profiles of these inhaled insulins were more or less comparable with that of rapid-acting insulin analogues. This is clearly different with TI which exhibits a strong metabolic effect shortly after application and a rapid decline in the metabolic effect thereafter; probably the duration of action is

  19. Aspartame and Its Analogues

    NASA Astrophysics Data System (ADS)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  20. Germananes: Germanium Graphane Analogues

    NASA Astrophysics Data System (ADS)

    Goldberger, Joshua

    2014-03-01

    Graphene's success has shown that it is not only possible to create stable, single-atom thick sheets from a crystalline solid, but that these materials have fundamentally different properties than the parent material. Our interest focuses on the synthesis and properties of Group IV graphane analogues. We have synthesized for the first time, mm-scale crystals of a hydrogen-terminated germanium multilayered graphane analogue (germanane, GeH) from the topochemical deintercalation of CaGe2. This layered van der Waals solid is analogous to multilayered graphane. The surface layer of GeH only slowly oxidizes in air over the span of five months, while the underlying layers are resilient to oxidation. We demonstrate that it is possible to covalently terminate the external surface with organic substituents to tune the electronic structure, and enhance the stability. These materials represent a new class of covalently terminated graphane analogues having great potential for a wide range of optoelectronic and sensing applications, especially since theory predicts a direct band gap of 1.53 eV and an electron mobility of 18,000 cm2/Vs which is five times higher than that of bulk Ge.

  1. Quantum analogue computing.

    PubMed

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  2. Anti-insulin antibody test

    MedlinePlus

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  3. Excitation of thermoacoustic oscillations by small premixed flames

    SciTech Connect

    Coats, C.M.; Chang, Z.; Williams, P.D.

    2010-06-15

    Experiments have been carried out in which very small lean premixed flames closely representative of those formed by modern multiport domestic gas burners have been subjected to controlled acoustic perturbation. PLIF from CH has been used to visualise the flame response and the heat-release-rate fluctuations have been evaluated directly from the flame images. It is shown that small laminar flames can amplify the effects of acoustic velocity fluctuations by mechanisms that do not involve resonant heat loss to the burner and that the fluctuations in flame-front area are not adequately characterised by a Strouhal number alone. The measured transfer function is compared with the predictions of various analytical formulations and a new model of the flame oscillation is proposed which applies specifically to situations in which the design of the burner renders the flame base immobile. (author)

  4. Turbulent premixed combustion; Further discussions on the scales of fluctuations

    SciTech Connect

    Borghi, R. )

    1990-06-01

    The prediction of turbulent combustion is classically performed by numerical integration of modeled equations. For each existing approach, a crucial quantity is a time scale for the destruction of temperature (or concentration) fluctuations. Usually, this time scale is simply taken as proportional to the corresponding time scale for velocity fluctuations, but the question of the influence of the reaction on this scale arises, and has already been discussed. The authors discuss this point in the particular case of wrinkled premixed flames. Algebraic closure formulas, as well as closures based on the so-called {epsilon}{sub y} equation, or on the equation for the flame surface by unit of volume of Marble and Broadwell, are proposed and discussed. It is found, in particular, that in the case of wrinkled flames with infinite Damkohler and Reynolds numbers the reaction does not play any direct role on the time scale.

  5. A numerical investigation of premixed combustion in wave rotors

    NASA Technical Reports Server (NTRS)

    Nalim, M. Razi; Paxson, Daniel E.

    1996-01-01

    Wave rotor cycles which utilize premixed combustion processes within the passages are examined numerically using a one-dimensional CFD-based simulation. Internal-combustion wave rotors are envisioned for use as pressure-gain combustors in gas turbine engines. The simulation methodology is described, including a presentation of the assumed governing equations for the flow and reaction in the channels, the numerical integration method used, and the modeling of external components such as recirculation ducts. A number of cycle simulations are then presented which illustrate both turbulent-deflagration and detonation modes of combustion. Estimates of performance and rotor wall temperatures for the various cycles are made, and the advantages and disadvantages of each are discussed.

  6. Interaction of a vortex and a premixed flame

    NASA Technical Reports Server (NTRS)

    Ferziger, Joel H.; Rutland, Christopher J.

    1989-01-01

    The interaction of a vortex structure and a premixed flame is studied. The presence of pressure gradients in the vortex and density gradients in the flame result in a complicated interaction. This interaction has been examined when the flame and vortex are fully coupled and in two special cases where they are decoupled: a frozen flame case and a frozen vortex case. In the frozen flame case the main effect of the flame on the vortex is through the barocline torque term. This has been modeled for high Damkoehler numbers. In the frozen vortex case the main effect, at moderate Damkoehler numbers, is to convect the flame around the vortex. At low Damkoehler numbers, depending on the length scales, pockets of unburned gas can form or the flame structure can be significantly changed. The two frozen cases provide a basis for understanding the full interaction.

  7. Numerical simulation of premixed H2-air cellular tubular flames

    NASA Astrophysics Data System (ADS)

    Hall, Carl Alan; Wendell Pitz, Robert

    2016-03-01

    The detailed flame structure of laminar premixed cellular flames in the tubular domain is simulated in 2D using a fully-implicit primitive variable finite difference formulation that includes multicomponent transport and detailed chemical kinetics. Numerical results for H2/air flames are presented and compared against spatially resolved experimental measurements of temperature and chemical species including atomic H and OH. The experimental results compare well for flame structure and cell number, despite the numerical model under-predicting the peak temperature by 200 K. Numerical experiments were performed to assess the ability for cellular tubular flames to impact experimental and numerical investigations of practical flames. The cellular flame structure is found to provide a highly sensitive geometry that is useful for validating diffusive transport modelling approximations. This capability is exemplified through the development of a simple and accurate approximation for thermal diffusion (i.e. the Soret effect) that is suitable for practical combustion codes.

  8. Accelerative propagation and explosion triggering by expanding turbulent premixed flames.

    PubMed

    Akkerman, V'yacheslav; Chaudhuri, Swetaprovo; Law, Chung K

    2013-02-01

    The dynamics and morphology of outwardly propagating, accelerating turbulent premixed flames and the effect of flame acceleration on explosion triggering are analyzed. Guided by recent theoretical results and substantiated by experiments, we find that an expanding flame front in an externally forced, near-isotropic turbulent environment exhibits accelerative propagation given by a well-defined power law based on the average global flame radius. In this context the limits of the power-law exponent and the effective turbulence intensity experienced by the flame are derived. The power-law exponent is found to be substantially larger than that for the hydrodynamically unstable cellular laminar flames, hence facilitating the possibility of detonation triggering in turbulent environments. For large length scales, hydrodynamic instability is expected to provide additional acceleration, thus further favoring the attainment of detonation triggering.

  9. Premixed flame propagation in combustible particle cloud mixtures

    NASA Technical Reports Server (NTRS)

    Seshadri, K.; Yang, B.

    1993-01-01

    The structures of premixed flames propagating in combustible systems, containing uniformly distributed volatile fuel particles, in an oxidizing gas mixtures is analyzed. The experimental results show that steady flame propagation occurs even if the initial equivalence ratio of the combustible mixture based on the gaseous fuel available in the particles, phi(u) is substantially larger than unity. A model is developed to explain these experimental observations. In the model it is presumed that the fuel particles vaporize first to yield a gaseous fuel of known chemical composition which then reacts with oxygen in a one-step overall process. It is shown that the interplay of vaporization kinetics and oxidation process, can result in steady flame propagation in combustible mixtures where the value of phi(u) is substantially larger than unity. This prediction is in agreement with experimental observations.

  10. Coaxial fuel and air premixer for a gas turbine combustor

    DOEpatents

    York, William D; Ziminsky, Willy S; Lacy, Benjamin P

    2013-05-21

    An air/fuel premixer comprising a peripheral wall defining a mixing chamber, a nozzle disposed at least partially within the peripheral wall comprising an outer annular wall spaced from the peripheral wall so as to define an outer air passage between the peripheral wall and the outer annular wall, an inner annular wall disposed at least partially within and spaced from the outer annular wall, so as to define an inner air passage, and at least one fuel gas annulus between the outer annular wall and the inner annular wall, the at least one fuel gas annulus defining at least one fuel gas passage, at least one air inlet for introducing air through the inner air passage and the outer air passage to the mixing chamber, and at least one fuel inlet for injecting fuel through the fuel gas passage to the mixing chamber to form an air/fuel mixture.

  11. Flashback detection sensor for lean premix fuel nozzles

    DOEpatents

    Thornton, Jimmy Dean [Morgantown, WV; Richards, George Alan [Morgantown, WV; Straub, Douglas L [Morgantown, WV; Liese, Eric Arnold [Morgantown, WV; Trader, Jr., John Lee; Fasching, George Edward [Morgantown, WV

    2002-08-06

    A sensor for detecting the flame occurring during a flashback condition in the fuel nozzle of a lean premix combustion system is presented. The sensor comprises an electrically isolated flashback detection electrode and a guard electrode, both of which generate electrical fields extending to the walls of the combustion chamber and to the walls of the fuel nozzle. The sensor is positioned on the fuel nozzle center body at a location proximate the entrance to the combustion chamber of the gas turbine combustion system. The sensor provides 360.degree. detection of a flashback inside the fuel nozzle, by detecting the current conducted by the flame within a time frame that will prevent damage to the gas turbine combustion system caused by the flashback condition.

  12. Dynamics of premixed hydrogen/air flames in mesoscale channels

    SciTech Connect

    Pizza, Gianmarco; Frouzakis, Christos E.; Boulouchos, Konstantinos; Mantzaras, John; Tomboulides, Ananias G.

    2008-10-15

    Direct numerical simulation with detailed chemistry and transport is used to study the stabilization and dynamics of lean ({phi}=0.5) premixed hydrogen/air atmospheric pressure flames in mesoscale planar channels. Channel heights of h=2, 4, and 7 mm, and inflow velocities in the range 0.3{<=}U{sub IN}{<=}1100cm/ s are investigated. Six different burning modes are identified: mild combustion, ignition/extinction, closed steady symmetric flames, open steady symmetric flames, oscillating and, finally, asymmetric flames. Chaotic behavior of cellular flame structures is observed for certain values of U{sub IN}. Stability maps delineating the regions of the different flame types are finally constructed. (author)

  13. Flame surface density and burning rate in premixed turbulent flames

    SciTech Connect

    Shepherd, I.G.

    1995-10-01

    The flame surface density has been measured in hydrocarbon/air stagnation point and v-shaped premixed turbulent flames. A method is proposed to determine the flame surface density from the data obtained by laser sheet tomography. The average flame length and flame zone area as a function of the progress variable are calculated from a map of progress variable and a set of flame edges obtained from the tomographs. From these results a surface density estimate in two dimensions is determined. By this technique it is possible to avoid the difficulties which arise when using an algebraic model based on the measurement of the flame front geometry and a scalar length scale. From these results the burning rate can be obtained which compares well with estimates calculated using the fractal technique. The present method, however, is not constrained by a minimum window size as is the case for the fractal determinations.

  14. Behaviour of a Premixed Flame Subjected to Acoustic Oscillations

    PubMed Central

    Qureshi, Shafiq R.; Khan, Waqar A.; Prosser, Robert

    2013-01-01

    In this paper, a one dimensional premixed laminar methane flame is subjected to acoustic oscillations and studied. The purpose of this analysis is to investigate the effects of acoustic perturbations on the reaction rates of different species, with a view to their respective contribution to thermoacoustic instabilities. Acoustically transparent non reflecting boundary conditions are employed. The flame response has been studied with acoustic waves of different frequencies and amplitudes. The integral values of the reaction rates, the burning velocities and the heat release of the acoustically perturbed flame are compared with the unperturbed case. We found that the flame's sensitivity to acoustic perturbations is greatest when the wavelength is comparable to the flame thickness. Even in this case, the perturbations are stable with time. We conclude that acoustic fields acting on the chemistry do not contribute significantly to the emergence of large amplitude pressure oscillations. PMID:24376501

  15. Pre-mixing apparatus for a turbine engine

    DOEpatents

    Lacy, Benjamin Paul [Greer, SC; Varatharajan, Balachandar [Cincinnati, OH; Ziminsky, Willy Steve [Simpsonville, SC; Kraemer, Gilbert Otto [Greer, SC; Yilmaz, Ertan [Albany, NY; Melton, Patrick Benedict [Horse Shoe, NC; Zuo, Baifang [Simpsonville, SC; Stevenson, Christian Xavier [Inman, SC; Felling, David Kenton [Greenville, SC; Uhm, Jong Ho [Simpsonville, SC

    2012-04-03

    A pre-mixing apparatus for a turbine engine includes a main body having an inlet portion, an outlet portion and an exterior wall that collectively establish at least one fluid delivery plenum, and a plurality of fluid delivery tubes extending through at least a portion of the at least one fluid delivery plenum. Each of the plurality of fluid delivery tubes includes at least one fluid delivery opening fluidly connected to the at least one fluid delivery plenum. With this arrangement, a first fluid is selectively delivered to the at least one fluid delivery plenum, passed through the at least one fluid delivery opening and mixed with a second fluid flowing through the plurality of fluid delivery tubes prior to being combusted in a combustion chamber of a turbine engine.

  16. Internal combustion engine using premixed combustion of stratified charges

    DOEpatents

    Marriott, Craig D [Rochester Hills, MI; Reitz, Rolf D [Madison, WI

    2003-12-30

    During a combustion cycle, a first stoichiometrically lean fuel charge is injected well prior to top dead center, preferably during the intake stroke. This first fuel charge is substantially mixed with the combustion chamber air during subsequent motion of the piston towards top dead center. A subsequent fuel charge is then injected prior to top dead center to create a stratified, locally richer mixture (but still leaner than stoichiometric) within the combustion chamber. The locally rich region within the combustion chamber has sufficient fuel density to autoignite, and its self-ignition serves to activate ignition for the lean mixture existing within the remainder of the combustion chamber. Because the mixture within the combustion chamber is overall premixed and relatively lean, NO.sub.x and soot production are significantly diminished.

  17. Embedded computer controlled premixing inline injection system for air-assisted variable-rate sprayers

    USDA-ARS?s Scientific Manuscript database

    Improvements to reduce chemical waste and environmental pollution for variable-rate sprayers used in orchards and ornamental nurseries require inline injection techniques. A microprocessor controlled premixing inline injection system implementing a ceramic piston chemical metering pump and two small...

  18. An Investigation of a Hybrid Mixing Model for PDF Simulations of Turbulent Premixed Flames

    NASA Astrophysics Data System (ADS)

    Zhou, Hua; Li, Shan; Wang, Hu; Ren, Zhuyin

    2015-11-01

    Predictive simulations of turbulent premixed flames over a wide range of Damköhler numbers in the framework of Probability Density Function (PDF) method still remain challenging due to the deficiency in current micro-mixing models. In this work, a hybrid micro-mixing model, valid in both the flamelet regime and broken reaction zone regime, is proposed. A priori testing of this model is first performed by examining the conditional scalar dissipation rate and conditional scalar diffusion in a 3-D direct numerical simulation dataset of a temporally evolving turbulent slot jet flame of lean premixed H2-air in the thin reaction zone regime. Then, this new model is applied to PDF simulations of the Piloted Premixed Jet Burner (PPJB) flames, which are a set of highly shear turbulent premixed flames and feature strong turbulence-chemistry interaction at high Reynolds and Karlovitz numbers. Supported by NSFC 51476087 and NSFC 91441202.

  19. Sintering Response of Aluminum 6061-TiB2 Composite: Effect of Prealloyed and Premixed Matrix

    NASA Astrophysics Data System (ADS)

    Paidpilli, Mahesh; Gupta, Gaurav Kumar; Upadhyaya, Anish

    2017-09-01

    In the present study, Al6061-based alloy and composites were produced using powder metallurgy route. Two different kinds of base powders (prealloyed and premixed 6061Al alloy) were mixed with TiB2 particles in compositions ranging from 0 to 15 vol.%, respectively. The processed powders were compacted at 300 MPa and sintered at 620 °C under N2 atmosphere. The microstructural evolution of prealloyed and premixed 6061Al alloy, at different stages of sintering cycle, was studied using scanning electron microscope and EDS analysis. A comparative study was done between prealloyed- and premixed-based composites on the basis of densification, microstructure, hardness, transverse rupture strength and electrical conductivity as a function of TiB2 content. Results indicated that premixed-based composites have better mechanical properties than prealloyed-based composites.

  20. Preflame zone structure and main features of fuel conversion in atmospheric pressure premixed laminar hydrocarbon flames

    SciTech Connect

    Ksandopulo, G.I.

    1995-08-25

    This report describes the structure study of the premixed hydrocarbon-oxidizer Bunsen flames burning at the atmospheric pressure and also the ones with some inhibitors added. Studies were performed on hexane, propane, methane, acetylene, and hexene flames.

  1. Extinction conditions of a premixed flame in a channel

    SciTech Connect

    Alliche, Mounir; Haldenwang, Pierre; Chikh, Salah

    2010-06-15

    A local refinement method is used to numerically predict the propagation and extinction conditions of a premixed flame in a channel considering a thermodiffusive model. A local refinement method is employed because of the numerous length scales that characterize this phenomenon. The time integration is self adaptive and the solution is based on a multigrid method using a zonal mesh refinement in the flame reaction zone. The objective is to determine the conditions of extinction which are characterized by the flame structure and its properties. We are interested in the following properties: the curvature of the flame, its maximum temperature, its speed of propagation and the distance separating the flame from the wall. We analyze the influence of heat losses at the wall through the thermal conductivity of the wall and the nature of the fuel characterized by the Lewis number of the mixture. This investigation allows us to identify three propagation regimes according to heat losses at the wall and to the channel radius. The results show that there is an intermediate value of the radius for which the flame can bend and propagate provided that its curvature does not exceed a certain limit value. Indeed, small values of the radius will choke the flame and extinguish it. The extinction occurs if the flame curvature becomes too small. Furthermore, this study allows us to predict the limiting values of the heat loss coefficient at extinction as well as the critical value of the channel radius above which the premixed flame may propagate without extinction. A dead zone of length 2-4 times the flame thickness appears between the flame and the wall for a Lewis number (Le) between 0.8 and 2. For small values of Le, local extinctions are observed. (author)

  2. Premixed-Gas Flame Propagation in Hele-Shaw Cells

    NASA Technical Reports Server (NTRS)

    Sharif, J.; Abid, M.; Ronney, P. D.

    1999-01-01

    It is well known that buoyancy and thermal expansion affect the propagation ra and shapes of premixed gas flames. The understanding of such effects is complicated by the large density ratio between the reactants and products, which induces a baroclinic production of vorticity due to misalignment of density and pressure gradients at the front, which in turn leads to a complicated multi-dimensional flame/flow interaction. The Hele-Shaw cell, i.e., the region between closely-spaced flat parallel plates, is probably the simplest system in which multi-dimensional convection is presents consequently, the behavior of fluids in this system has been studied extensively (Homsy, 1987). Probably the most important characteristic of Hele-Shaw flows is that when the Reynolds number based on gap width is sufficiently small, the Navier-Stokes equations averaged over the gap reduce to a linear relation, namely a Laplace equation for pressure (Darcy's law). In this work, flame propagation in Hele-Shaw cells is studied to obtain a better understanding of buoyancy and thermal expansion effects on premixed flames. This work is also relevant to the study of unburned hydrocarbon emissions produced by internal combustion engines since these emissions are largely a result of the partial burning or complete flame quenching in the narrow, annular gap called the "crevice volume" between the piston and cylinder walls (Heywood, 1988). A better understanding of how flames propagate in these volumes through experiments using Hele-Shaw cells could lead to identification of means to reduce these emissions.

  3. Bioavailability of insulin detemir and human insulin at the level of peripheral interstitial fluid in humans, assessed by open-flow microperfusion.

    PubMed

    Bodenlenz, M; Ellmerer, M; Schaupp, L; Jacobsen, L V; Plank, J; Brunner, G A; Wutte, A; Aigner, B; Mautner, S I; Pieber, T R

    2015-12-01

    To find an explanation for the lower potency of insulin detemir observed in humans compared with unmodified human insulin by investigating insulin detemir and human insulin concentrations directly at the level of peripheral insulin-sensitive tissues in humans in vivo. Euglycaemic-hyperinsulinaemic clamp experiments were performed in healthy volunteers. Human insulin was administered i.v. at 6 pmol/kg/min and insulin detemir at 60 pmol/kg/min, achieving a comparable steady-state pharmacodynamic action. In addition, insulin detemir was doubled to 120 pmol/kg/min. Minimally invasive open-flow microperfusion (OFM) sampling methodology was combined with inulin calibration to quantify human insulin and insulin detemir in the interstitial fluid (ISF) of subcutaneous adipose and skeletal muscle tissue. The human insulin concentration in the ISF was ∼115 pmol/l or ∼30% of the serum concentration, whereas the insulin detemir concentration in the ISF was ∼680 pmol/l or ∼2% of the serum concentration. The molar insulin detemir interstitial concentration was five to six times higher than the human insulin interstitial concentration and metabolic clearance of insulin detemir from serum was substantially reduced compared with human insulin. OFM proved useful for target tissue measurements of human insulin and the analogue insulin detemir. Our tissue data confirm a highly effective retention of insulin detemir in the vascular compartment. The higher insulin detemir relative to human insulin tissue concentrations at comparable pharmacodynamics, however, indicate that the lower potency of insulin detemir in humans is attributable to a reduced effect in peripheral insulin-sensitive tissues and is consistent with the reduced in vitro receptor affinity. © 2015 John Wiley & Sons Ltd.

  4. Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed vs Premixed Parenteral Nutrition.

    PubMed

    Busch, Rebecca A; Curtis, Caitlin S; Leverson, Glen E; Kudsk, Kenneth A

    2015-07-01

    Parenteral nutrition (PN) is available as individualized prescriptions frequently prepared with an automated compounding device or as commercially prepared premixed solutions. Our institution exclusively used individualized PN until an amino acid shortage forced a temporary switch to premixed solutions. In general, premixed solutions contain lower electrolyte levels than individualized formulations prescribed for patients with normal organ function. We aimed to quantify supplemental intravenous piggyback (IVPB) electrolyte use in adult patients receiving individualized and premixed PN and to quantify any effect on difference in the cost of therapy. We compared use of supplemental IVPB electrolytes administered to patients receiving PN during consecutive periods prior to and during the amino acid shortage. Electrolyte IVPBs tabulated were potassium chloride, 10 and 20 mEq; magnesium sulfate, 2 g and 4 g; potassium phosphate, 7.5 and 15 mmol; and sodium phosphate, 7.5 and 15 mmol IVPB. There was no statistical difference in the number of PN formulations administered per day during each period (14.7 ± 3.9 vs 14.0 ± 2.6, individualized vs premixed, respectively). Total IVPB electrolytes prescribed per day increased significantly from the individualized PN period to the premixed PN period (7.03 ± 3.8 vs 13.8 ± 6.8; P < .0001). The additional IVPB electrolyte supplementation required in patients receiving premixed PN was associated with an additional $11,855.74 cost per 30 days of therapy compared with those who received individualized PN. Inpatient use of premixed PN results in a significant increase in IVPB electrolyte supplementation and cost compared with individualized PN use. © 2014 American Society for Parenteral and Enteral Nutrition.

  5. Premixed, injectable PLA-modified calcium deficient apatite biocement (cd-AB) with washout resistance.

    PubMed

    Wu, Fan; Ngothai, Yung; Wei, Jie; Liu, Changsheng; O'Neill, Brian; Wu, Yuequn

    2012-04-01

    By using a non-aqueous solution as the mixing liquid, the washout resistance of the calcium deficient apatite biocement (cd-AB) was significantly improved, over that of the conventional method of using cd-AB with water as the liquid phase. In this study, premixed and injectable cd-AB was prepared, which had the advantage of being stable in the syringe and hardens only after being delivered to the defect area. The cd-AB powder with a Ca/P ratio of 1.5 consists of a mixture of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA). A solution of polylactide (PLA) in N-methyl-2-pyrrolidone (NMP) was used as the liquid phase of the premixed cd-AB. The premixed cd-AB paste injected into an aqueous environment exhibited excellent washout resistance. The premixed cd-AB had longer setting time and lower compressive strength than conventional cd-AB. The hydration products of premixed cd-AB were a mixture of calcium deficient hydroxyapatite (cd-HA) and PLA. In vitro Tris-HCl immersion tests demonstrated that the premixed cd-AB could be degradable. The results revealed that the premixed cd-AB was cytocompatible and had no adverse effects on the attachment and proliferation of MG-63 osteoblast-like cells in vitro. The most distinct advantages of premixed and injectable PLA-modified cd-AB were its excellent washout resistance and in vitro degradability, suggesting that it may be a promising candidate for bone repair.

  6. Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed versus Premixed Parenteral Nutrition

    PubMed Central

    Busch, Rebecca A.; Curtis, Caitlin S.; Leverson, Glen E.; Kudsk, Kenneth A.

    2014-01-01

    Background Parenteral nutrition (PN) is available as individualized prescriptions frequently prepared with an automated compounding device, or as commercially prepared premixed solutions. Our institution exclusively used individualized PN until an amino acid shortage forced a temporary switch to premixed solutions. In general, premixed solutions contain lower electrolyte levels than individualized formulations prescribed for patients with normal organ function. We aimed to quantify supplemental intravenous piggyback (IVPB) electrolyte use in adult patients receiving individualized and premixed PN, and to quantify any effect on difference in the cost of therapy. Methods We compared use of supplemental IVPB electrolytes administered to patients receiving PN during consecutive periods prior to and during the amino acid shortage. Electrolyte IVPBs tabulated were: potassium chloride 10 and 20 mEq, magnesium sulfate 2 g and 4 g, potassium phosphate 7.5 and 15 mmol, sodium phosphate 7.5 and 15 mmol IVPB. Results There was no statistical difference in the number of PN formulations administered per day during each period (14.7 + 3.9 vs. 14.0 + 2.6, individualized vs. premixed, respectively). Total IVPB electrolytes prescribed per day increased significantly from the individualized PN period to the premixed PN period (7.03 + 3.8 vs. 13.8 + 6.8, p<0.0001). The additional IVPB electrolyte supplementation required in patients receiving premixed PN was associated with an additional $11,855.74 cost per 30 days of therapy compared to those who received individualized PN. Conclusion Inpatient use of premixed PN results in a significant increase in IVPB electrolyte supplementation and cost when compared to individualized PN use. PMID:24390715

  7. Metabolism of human insulin after subcutaneous administration: A possible means to uncover insulin misuse.

    PubMed

    Thomas, Andreas; Brinkkötter, Paul; Schänzer, Wilhelm; Thevis, Mario

    2015-10-15

    The misuse of insulin for performance enhancement in sport or as toxic agent has frequently been reported in the past. In contrast to synthetic insulin analogues, the administration of recombinant human insulin is hardly recognized by mass spectrometry. The present study was designed to uncover the misuse of recombinant human insulin for doping control purposes as well as for forensic applications. It is hypothesized that an altered metabolite profile of circulating insulin prevails after subcutaneous administration due to exposure of insulin to epidermal proteases. In vitro experiments with skin tissue lysates (S9 fraction and microsomes), different biological fluids (urine, serum, plasma) and recombinant human insulin were performed and the deriving metabolites were characterized by liquid chromatography coupled to high resolution mass spectrometry (HRMS). Afterwards, authentic blood samples of patients suffering from diabetes mellitus and a control group of healthy humans were analysed. Therefore, a method using protein precipitation, ultrafiltration and antibody-coated magnetic beads for purification with subsequent separation by nano-scale liquid chromatography coupled a Q Exactive mass spectrometer was applied. Several metabolites of insulin with C-terminally truncated sequences of the B-chain (and A-chain in minor extent) were identified within this study. Here, the DesB30 human insulin represents the major metabolite in all experiments. This metabolite is frequently found in urine samples due to degradation processes and, thus, disqualifies this matrix for the intended purposes. In contrast, blood samples do commonly not contain DesB30 insulin, which was corroborated by data obtained from the control group. In post-administration blood samples, minute but distinct amounts (approx. 50 pg mL(-1)) of DesB30 insulin were found and suggest the use of this analyte as potential marker for subcutaneous human insulin administration, supporting the attempts to

  8. The Behavior of Methane-Air Partially Premixed Flames Under Normal- and Zero-G Conditions

    NASA Technical Reports Server (NTRS)

    Puri, Ishwar K.; Aggarwal, Suresh K.; Choi, Chun Wai; Hegde, Uday

    2001-01-01

    Partially premixed flames (PPFs) represent a class of hybrid flames containing multiple reaction zones. These flames are established when less than stoichiometric quantity of oxidizer is molecularly mixed with the fuel stream before entering the reaction zone where additional oxidizer is available for complete combustion. This mode of combustion can be used to exploit the advantages of both nonpremixed and premixed flames regarding operational safety, lower pollutant emissions and flame stabilization. A double flame containing a fuel-rich premixed reaction zone, which is anchored by a nonpremixed reaction zone, is one example of a partially premixed flame. A triple flame is also a PPF that contains three reaction zones, namely, a fuel-rich premixed zone, a fuel-lean premixed zone, and a nonpremixed reaction zone. Herein we focus on two aspects of our investigation, one involving the development of optical diagnostics that can be used on a microgravity rig, which has been recently fabricated, and the other on the numerically predicted differences between normal- and zero-gravity PPFs. Both the measurements and simulations examine the detailed structure of methane-air PPFs stabilized on a Wolfhard-Parker slot burner.

  9. Insulin Degludec/Liraglutide: A Review in Type 2 Diabetes.

    PubMed

    Greig, Sarah L; Scott, Lesley J

    2015-09-01

    Insulin degludec/liraglutide (Xultophy(®)), a fixed-ratio combination of an ultra-long-acting insulin analogue and a glucagon-like protein-1 (GLP-1) receptor agonist, is available in the EU for the management of inadequately controlled type 2 diabetes. Once-daily subcutaneous insulin degludec/liraglutide as add-on therapy to oral antidiabetics was effective and generally well tolerated in adults with inadequately controlled type 2 diabetes in several well designed 26-week phase III trials. In insulin-naive patients, add-on insulin degludec/liraglutide provided significantly greater improvements in glycated haemoglobin (HbA1c) levels than add-on insulin degludec, liraglutide or placebo, or unchanged GLP-1 receptor agonists (i.e. liraglutide or exenatide). In the extension of one of these trials, the efficacy of add-on insulin degludec/liraglutide was maintained for a total of 52 weeks. In insulin-experienced patients, add-on insulin degludec/liraglutide was significantly more effective with regard to improvements in HbA1c levels than add-on insulin degludec (at equivalent doses) or ongoing insulin glargine therapy. Add-on insulin degludec/liraglutide was associated with a lower incidence of confirmed hypoglycaemia than add-on insulin degludec in insulin-naive patients or ongoing insulin glargine in insulin-experienced patients, and a lower initial rate of nausea than add-on liraglutide. Thus, once-daily subcutaneous insulin degludec/liraglutide is a useful add-on therapy option for adult patients with inadequately controlled type 2 diabetes.

  10. New insulins and newer insulin regimens: a review of their role in improving glycaemic control in patients with diabetes.

    PubMed

    Gururaj Setty, S; Crasto, W; Jarvis, J; Khunti, K; Davies, M J

    2016-03-01

    The legacy effect of early good glycaemic control in people with diabetes shows it is associated with reduction of microvascular and macrovascular complications. Insulin therapy is essential and lifesaving in individuals with type 1 diabetes and beneficial for those with type 2 diabetes who fail to achieve optimal glycaemic targets with other classes of glucose-lowering therapies. Since the introduction of insulin analogues, insulin management has changed. This follow-up review attempts to update our earlier publication from 2009 and discusses the role of new insulin analogues and newer insulin regimens. Recognising the advent of new quality and economic initiatives both in the UK and worldwide, this paper reviews current insulin prescribing and the pros and cons of prescribing analogues in comparison to the human insulins that are now gaining more acceptance in everyday clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  11. Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

    PubMed

    Kovil, Rajiv; Chawla, Manoj; Rajput, Rajesh; Singh, A K; Sinha, Binayak; Ghosal, Samit; Ballani, Piya; Gupta, Sunil; Tanna, Snehal; Bandukwala, S M; Shah, Tejas; Negalur, Vijay; Bhoraskar, Anil; Aravind, S R; Zargar, Abdul H; Kesavadev, Jothydev; Das, Ashok Kumar

    2017-02-01

    Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

  12. Diabetes and Insulin

    MedlinePlus

    ... in the abdomen just behind the stomach, produces insulin. Insulin is a hormone that takes glucose from the ... occurs when the pancreas does not produce enough insulin or when the body doesn’t use insulin ...

  13. Analogue-to-Digital and Digital-to-Analogue Conversion.

    ERIC Educational Resources Information Center

    Gregory, Martin

    1997-01-01

    Discusses circuits for three-bit and four-bit analogue digital converters and digital analogue converters. These circuits feature slow operating speeds that enable the circuitry to be used to demonstrate the mode of operation using oscilloscopes and signal generators. (DDR)

  14. Measurements and modeling of nitric oxide formation in counterflow, premixed, methane/oxygen/nitrogen flames

    NASA Astrophysics Data System (ADS)

    Thomsen, Duane Douglas

    1999-10-01

    Laser-induced fluorescence (LIF) measurements of NO concentration in a variety of CH4/O2/N2 flames are used to evaluate the chemical kinetics of NO formation. The analysis begins with previous measurements in flat, laminar, premixed CH4/O2/N 2 flames stabilized on a water-cooled McKenna burner at pressures ranging from 1 to 14.6 atm, equivalence ratios from 0.5 to 1.6, and volumetric nitrogen/oxygen dilution ratios of 2.2, 3.1 and 3.76. These measured results are compared to predictions to determine the capabilities and limitations of the comprehensive kinetic mechanism developed by the Gas Research Institute (GRI), version 2.11. The model is shown to predict well the qualitative trends of NO formation in lean-premixed flames, while quantitatively underpredicting NO concentration by 30-50%. For rich flames, the model is unable to even qualitatively match the experimental results. These flames were found to be limited by low temperatures and an inability to separate the flame from the burner surface. In response to these limitations, a counterflow burner was designed for use in opposed premixed flame studies. A new LIF calibration technique was developed and applied to obtain quantitative measurements of NO concentration in laminar, counterflow premixed, CH 4/O2/N2 flames at pressures ranging from 1 to 5.1 atm, equivalence ratios of 0.6 to 1.5, and an N2/O2 dilution ratio of 3.76. The counterflow premixed flame measurements are combined with measurements in burner-stabilized premixed flames and counterflow diffusion flames to build a comprehensive database for analysis of the GRI kinetic mechanism. Pathways, quantitative reaction path and sensitivity analyses are applied to the GRI mechanism for these flame conditions. The prompt NO mechanism is found to severely underpredict the amount of NO formed in rich premixed and nitrogen-diluted diffusion flames. This underprediction is traced to uncertainties in the CH kinetics as well as in the nitrogen oxidation chemistry

  15. Hydrodynamics of Spherical Flows and Geometry of Premixed Flames near the Stagnation Point of Axisymmetric Viscous Counterflows

    NASA Technical Reports Server (NTRS)

    Sohrab, Siavash H.

    1999-01-01

    Counterflow premixed flames play a significant role in the modeling of laminar flames. This is in part motivated by the fact that stretched premixed flames simulate local flamelet dynamics within turbulent premixed flames. In the present study, the modified form of the Navier-Stokes equation for reactive fields introduced earlier is employed to investigate the hydrodynamics of spherical flows embedded within counterflows. The geometry of premixed flames near the stagnation point is also determined. The predictions are in favorable agreement with the experimental observations and prior numerical studies.

  16. Insulin-Insulin-like Growth Factors Hybrids as Molecular Probes of Hormone:Receptor Binding Specificity.

    PubMed

    Křížková, Květoslava; Chrudinová, Martina; Povalová, Anna; Selicharová, Irena; Collinsová, Michaela; Vaněk, Václav; Brzozowski, Andrzej M; Jiráček, Jiří; Žáková, Lenka

    2016-05-31

    Insulin, insulin-like growth factors 1 and 2 (IGF-1 and -2, respectively), and their receptors (IR and IGF-1R) are the key elements of a complex hormonal system that is essential for the development and functioning of humans. The C and D domains of IGFs (absent in insulin) likely play important roles in the differential binding of IGF-1 and -2 to IGF-1R and to the isoforms of IR (IR-A and IR-B) and specific activation of these receptors. Here, we attempted to probe the impact of IGF-1 and IGF-2 D domains (DI and DII, respectively) and the IGF-2 C domain (CII) on the receptor specificity of these hormones. For this, we made two types of insulin hybrid analogues: (i) with the C-terminus of the insulin A chain extended by the amino acids from the DI and DII domains and (ii) with the C-terminus of the insulin B chain extended by some amino acids derived from the CII domain. The receptor binding affinities of these analogues and their receptor autophosphorylation potentials were characterized. Our results indicate that the DI domain has a more negative impact than the DII domain does on binding to IR, and that the DI domain Pro-Leu-Lys residues are important factors for a different IR-A versus IR-B binding affinity of IGF-1. We also showed that the additions of amino acids that partially "mimic" the CII domain, to the C-terminus of the insulin B chain, change the binding and autophosphorylation specificity of insulin in favor of the "metabolic" IR-B isoform. This opens new venues for rational enhancement of insulin IR-B specificity by modifications beyond the C-terminus of its B chain.

  17. Insulin Therapy

    MedlinePlus

    ... results yourself or insert the strip into a machine called an electronic glucose meter. The results will tell you whether or not your blood sugar is in a healthy range. Your doctor will give you additional information about monitoring your blood sugar.When should I take insulin? ...

  18. ODT Based Closure Model for Non-Premixed Combustion LES

    NASA Astrophysics Data System (ADS)

    Miles, Jeffery Scott

    An LES closure method for turbulent non-premixed combustion using data from standalone ODT simulations is developed and validated. An ODT simulation provides a complete view of turbulent combustion including detailed chemistry within a single dimension through spatially (in 1D) and temporally resolved solutions for thermo chemical scalars and a stochastic description of turbulent advection. A unique closure technique removes the limitations associated with prescribed FDF distributions by using the resolved ODT statistics to construct joint scalar distributions needed for LES closure. These distributions are combined with other ODT statistics to construct closure tables for filtered variables such as density and chemical source terms. The tabulated closure follows the classical integration over state-space combining joint distributions with statistics from dependent variables. The temperature and mixture fraction are considered for this joint FDF as they can be combined to provide a complete view of the chemical and thermal state of the overall system within a non-premixed combustion problem. The ODT simulations are used to extract filtered and unfiltered correlations representing FDF distributions for each of the state-defining scalars; and kernel density functions are used to convert the sample datasets into smooth distributions that represent FDFs found within ODT statistics. A stand-alone ODT simulation is configured to generate the statistics and data needed for the closure model construction. The ODT domain selected to match the target problem domain is a one-dimensional axisymmetric piloted jet. This configuration is capable of capturing many of the features of a turbulent jet diffusion flame much like a spatially resolved DNS simulation but at a fraction of the cost. For each realization, the state variables are filtered and stored in vector form with the "instantaneous" values for each term included in the unclosed set required in the LES domain. Model

  19. New ways of insulin delivery.

    PubMed

    Heinemann, L

    2010-02-01

    foresee that with most new ways of insulin delivery the bioavailability/biopotency will be lower than with subcutaneous (SC) insulin administration. This in turn requires that more insulin has to be applied to induce the same metabolic (blood glucose lowering) effect in patients with diabetes. If the costs of insulin are of relevance for the price (this clearly depends on the source of insulin the individual company has to use) the price of the product will be higher relative to standard SC insulin therapy. The question is, clearly, what are the advantages of the new product? In times when SC insulin administration was painful and cumbersome it was clear that the ease of swallowing an insulin tablet was a good argument for many patients. With the invention of thin insulin needles that make the SC injection practically pain free in most cases, this argument of being 'convenient' becomes of limited relevance. However, for many patients (especially the public) the avoidance of 'injection' is an argument. The question is, how much is the patient (society) willing to pay for such a psychological 'advantage'? Most probably additional clear-cut clinical advantages must be demonstrable to convince the payers to reimburse a new product, especially when the price is higher than that of SC insulin. If, for example, postprandial glycaemic excursions are considerably better controlled because the pharmacodynamic (PD) effects are better than with SC injection of rapid-acting insulin analogues (this might be possible with inhaled Technosphere insulin), this would be a clinically relevant argument. Without such advantages, new products will have no market success. Most probably it will not be until one of the various ARIA developments (e.g. nasal insulin) makes it into a financially attractive product (sufficient return on investment) that more money will flow again in this area of research. The search for relevant articles about new ways to deliver insulin did not reveal very many

  20. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  1. Short communication: Preference for flavored concentrate premixes by dairy cows.

    PubMed

    Harper, M T; Oh, J; Giallongo, F; Lopes, J C; Weeks, H L; Faugeron, J; Hristov, A N

    2016-08-01

    Flavor preferences may be used to stimulate feed intake in dairy cows, which may improve use of robotic milking systems and increase feed intake of sick cows. A cafeteria-design experiment was used to determine if dairy cows have flavor preferences. Sixteen lactating Holstein cows averaging 197±32d in milk, 1.9±0.8 lactations, 27.8±4.2kg/d of dry matter intake, and 41.5±7.4kg/d of milk yield were involved in the experiment. Cows were offered 7 flavored concentrate premixes (FCP) and 1 control premix. The FCP flavors were anise, fenugreek, honey, orange, thyme, molasses, and vanilla; the absence of flavor, neutral, acted as a control. The inclusion rate of the flavors in FCP was 250 to 300g/t on an as-is basis. Cows were not adapted to the flavors before the experiment. Cows were housed in a tiestall barn and offered, on each day, 4 different FCP (1kg each) in plastic bins placed in front of each cow. The experiment lasted 6 consecutive days. Each FCP was presented to each cow once every 2d, 2h after the morning feeding. Flavors and position of the bins in front of the cows were randomized. As a result, each flavor was presented to each cow 3 times during the experiment, at 3 different bin locations. Each cow had access to the FCP for 5min from the time they started eating. Eating time and amount eaten were recorded. The vanilla and fenugreek FCP were consumed the most, at 408 and 371g/5-min offering, respectively, whereas the orange and anise FCP were consumed the least, at 264 and 239g/5-min offering, respectively. Similarly, cows spent the most time eating the vanilla and fenugreek FCP at 99 and 75 s/offering, respectively, and the least amount of time eating the orange and anise FCP at 49 and 50 s/offering, respectively. We detected an effect of bin position: the 2 center FCP were consumed more than the outer 2 FCP. Flavor had no effect on consumption rate. In conclusion, relative to the control, concentrate intake was not affected by flavor, but dairy cows

  2. Partially-Premixed Flames in Internal Combustion Engines

    SciTech Connect

    Robert W. Pitz; Michael C. Drake; Todd D. Fansler; Volker Sick

    2003-11-05

    This was a joint university-industry research program funded by the Partnerships for the Academic-Industrial Research Program (PAIR). The research examined partially premixed flames in laboratory and internal combustion engine environments at Vanderbilt University, University of Michigan, and General Motors Research and Development. At Vanderbilt University, stretched and curved ''tubular'' premixed flames were measured in a unique optically accessible burner with laser-induced spontaneous Raman scattering. Comparisons of optically measured temperature and species concentration profiles to detailed transport, complex chemistry simulations showed good correspondence at low-stretch conditions in the tubular flame. However, there were significant discrepancies at high-stretch conditions near flame extinction. The tubular flame predictions were found to be very sensitive to the specific hydrogen-air chemical kinetic mechanism and four different mechanisms were compared. In addition, the thermo-diffusive properties of the deficient reactant, H2, strongly affected the tubular flame structure. The poor prediction near extinction is most likely due to deficiencies in the chemical kinetic mechanisms near extinction. At the University of Michigan, an optical direct-injected engine was built up for laser-induced fluorescence imaging experiments on mixing and combustion under stratified charge combustion conditions with the assistance of General Motors. Laser attenuation effects were characterized both experimentally and numerically to improve laser imaging during the initial phase of the gasoline-air mixture development. Toluene was added to the isooctane fuel to image the fuel-air equivalence ratio in an optically accessible direct-injected gasoline engine. Temperature effects on the toluene imaging of fuel-air equivalence ratio were characterized. For the first time, oxygen imaging was accomplished in an internal combustion engine by combination of two fluorescence trackers

  3. Catalysis of propane oxidation and premixed propane-air flames

    NASA Astrophysics Data System (ADS)

    Wiswall, James T.

    Improvements in deriving energy from hydrocarbon fuels will have a large impact on our efforts to transition to sustainable and renewable energy resources. The hypothesis for this work is that catalysis can extend the useful operating conditions for hydrocarbon oxidation and combustion, improve device efficiencies, and reduce pollutants. Catalysis of propane oxidation and premixed propane-air flames are examined experimentally, using a stagnation-flow reactor to identify the important physical and chemical mechanisms over a range of flow catalyst, and temperature conditions. The propane oxidation studies consider five catalyst materials: platinum, palladium, SnO2, 90% SnO2 -- 10% Pt (by mass), and quartz. The volume fractions of CO2, O2, C 3H8, CO, NO and the electric power required to control the catalyst temperature quantify the activity of each catalyst for the equivalence ratios of φ = 0.67, 1.00, and 1.50, and over the catalyst temperature range 23-800°C. Quartz is used as a baseline and confirmed to be non-reactive at all conditions. 100% SnO2 has minimal reactivity. Platinum, palladium, and 90% SnO2 -- 10% Pt show similar trends and have the highest catalytic activity at φ = 1.50. Palladium and 90% SnO 2 -- 10% Pt show an increasing catalyst-activation temperature (Tsa) for decreasing φ, and platinum shows an approximately constant catalyst-activation temperature for decreasing φ (Tsa = 310°C). Of these the 90% SnO2 -- 10% Pt catalyst shows the lowest Tsa, occurring for the φ = 1.5 mixture (Tsa = 250°C). The studies of premixed propane-air flames consider platinum and quartz stagnation surfaces for fuel-mixture velocities from 0.6-1.6 m/s. Five flame structures are observed: cool core envelope, cone, envelope, disk and ring flames. The lean-extinction limit, disk-to-ring flame transition φ, and the disk-flame to stagnation-plane distance are reported. Platinum inhibits the ring flame structure. The lean-extinction limit and disk-flame to stagnation

  4. Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis

    PubMed Central

    Freemantle, Nick; Chou, Engels; Frois, Christian; Zhuo, Daisy; Lehmacher, Walter; Vlajnic, Aleksandra; Wang, Hongwei; Chung, Hsing-wen; Zhang, Quanwu; Wu, Eric; Gerrits, Charles

    2016-01-01

    Objective To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). Design This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. Outcome measures Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. Results 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: −0.08; 95% credible interval (CrI): −0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; −0.28 to 0.32), degludec (−0.12; −0.42 to 0.20) and premixed insulin (0.26; −0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; −0.31 to 1.71), NPH (−0.76; −1.75 to 0.21) and degludec (−0.63; −1.63 to 0.35), but significantly lower compared with premixed insulin (−1.83; −2.85 to −0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. Conclusions NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia

  5. Unstrained and strained flamelets for LES of premixed combustion

    NASA Astrophysics Data System (ADS)

    Langella, Ivan; Swaminathan, Nedunchezhian

    2016-05-01

    The unstrained and strained flamelet closures for filtered reaction rate in large eddy simulation (LES) of premixed flames are studied. The required sub-grid scale (SGS) PDF in these closures is presumed using the Beta function. The relative performances of these closures are assessed by comparing numerical results from large eddy simulations of piloted Bunsen flames of stoichiometric methane-air mixture with experimental measurements. The strained flamelets closure is observed to underestimate the burn rate and thus the reactive scalars mass fractions are under-predicted with an over-prediction of fuel mass fraction compared with the unstrained flamelet closure. The physical reasons for this relative behaviour are discussed. The results of unstrained flamelet closure compare well with experimental data. The SGS variance of the progress variable required for the presumed PDF is obtained by solving its transport equation. An order of magnitude analysis of this equation suggests that the commonly used algebraic model obtained by balancing source and sink in this transport equation does not hold. This algebraic model is shown to underestimate the SGS variance substantially and the implications of this variance model for the filtered reaction rate closures are highlighted.

  6. Premixed flame response to unsteady strain-rate and curvature

    SciTech Connect

    Najm, H.N.; Wyckoff, P.S.

    1996-05-01

    The interaction of a premixed stoichiometric methane-air flame with a counter-rotating vortex-pair is studied using a skeletal C{sub 1} chemical description of the reaction process. The focus is on the modification to flame structure and dynamics due to unsteady strain-rate and curvature. The detailed description of flame structure and dynamics in response to unsteady flow is necessary to establish relevant extinction criteria in unsteady multi-dimensional flow, which, based on recent experimental evidence, may be significantly different from those of steady one-dimensional counterflow stagnation flames. Present results suggest that the increasing unsteady tangential strain-rate causes modification of flame structure that leads to reduced reaction rates of key chain-branching reactions which are active on the products side of the flame. This causes a reduction in the concentrations of active radicals, such as H, OH, and O, which are necessary for the breakdown of hydrocarbons on the reactants side of the flame.

  7. Development of a lean premixed burner for hydrogen utilization

    SciTech Connect

    Keller, J.O.

    1996-10-01

    The long-term mandate of the hydrogen program is to develop the technologies needed to establish a hydrogen economy. Although a hydrogen fueled automobile has been established as a demonstration project, there are at least three other end use sectors that are recognized by the H{sub 2} program and that are addressed by this project. These end uses are: (1) power generation from stationary turbines, (2) generation of process heat or steam, and (3) commercial and residential direct use applications. Eliminating carbon from the fuel will remove carbon containing species from the emissions, however, NO{sub x} resulting from thermal NO production cannot be ignored. Thermal NO production is minimized by reducing the peak combustion temperature and the residence time at the peak temperature. NO can be reduced to extremely low levels (a few ppm) by operating sufficiently lean to reduce the peak combustion temperatures below 1700 to 1800 K. The objectives for this project are to: (1) develop an environmentally benign and safe burner operating on hydrogen in a lean premixed mode, (2) provide a facility in which fundamental investigations can be performed to support other programs.

  8. Rayleigh-Taylor Instability in non-premixed reacting flames.

    NASA Astrophysics Data System (ADS)

    Attal, Nitesh; Ramaprabhu, Praveen

    2015-11-01

    The Rayleigh-Taylor instability (RTI) occurs at a perturbed interface between fluids of different densities when a light fluid pushes a heavier fluid. The mixing driven by RTI affects several physical phenomena, such as Inertial Confinement Fusion, Supernovae detonation, centrifugal combustors and liquid rocket engines. The RTI in such flows is often coupled with chemical/nuclear reactions that may form complex density stratifications in the form of flames or ablative layers. We investigate such a non-premixed fuel-air interface subject to a constant acceleration and developing under the influence of chemical reactions using high-resolution, Navier-Stokes simulations. The H2 fuel is diluted with N2 to vary the density difference across the interface in thermal equilibrium (at 1000K). The intervening layer between fuel and air is subject to exothermic combustion reactions to form a flame. Following combustion, initially unstable fuel-air interfaces at an Atwood number (At) <0.5, transform into stable (fuel-flame) and unstable (flame-air) interfaces. We report on interfaces (At = 0.2 and 0.6) with single wavelength, sinusoidal perturbations and a broadband spectrum of multimode perturbations.

  9. A ring stabilizer for lean premixed turbulent flames

    SciTech Connect

    Johnson, M.R.; Kostiuk, L.W.; Cheng, R.K.

    1998-08-01

    In previous experiments on conical flame behavior in microgravity, which were conducted in drop-towers and in airplanes, the use of a pilot flame was not an option. To permit combustion of stable lean premixed conical flames without a pilot, a ring stabilizer was developed. Although similar types of bluff-body stabilization have been used in the past, the ring stabilizer is somewhat unique. It is designed to fit inside the burner exit port and has demonstrated to be highly effective in stabilizing flames over a very wide range of conditions (including ultra-lean flames at high flow-rates) without adversely affecting flame emissions. Unlike a simple rod stabilizer or a stagnation flame system, the benefit of having the stabilizer conform to the burner port is that there is very little leakage of the unburned fuel. The purpose of this brief communication is to offer this simple and highly useful device to the combustion research community. Presented are highlights of a parametric study that measured the stabilization limits and pollutant emissions of several different rings, and demonstrated their potential for use in practical systems.

  10. On flame kernel formation and propagation in premixed gases

    SciTech Connect

    Eisazadeh-Far, Kian; Metghalchi, Hameed; Parsinejad, Farzan; Keck, James C.

    2010-12-15

    Flame kernel formation and propagation in premixed gases have been studied experimentally and theoretically. The experiments have been carried out at constant pressure and temperature in a constant volume vessel located in a high speed shadowgraph system. The formation and propagation of the hot plasma kernel has been simulated for inert gas mixtures using a thermodynamic model. The effects of various parameters including the discharge energy, radiation losses, initial temperature and initial volume of the plasma have been studied in detail. The experiments have been extended to flame kernel formation and propagation of methane/air mixtures. The effect of energy terms including spark energy, chemical energy and energy losses on flame kernel formation and propagation have been investigated. The inputs for this model are the initial conditions of the mixture and experimental data for flame radii. It is concluded that these are the most important parameters effecting plasma kernel growth. The results of laminar burning speeds have been compared with previously published results and are in good agreement. (author)

  11. Lean premixed flames for low NO{sub x} combustors

    SciTech Connect

    Sojka, P.; Tseng, L.; Bryyjak, J.

    1995-12-31

    The overall objectives of the research at Purdue are to: obtain a reduced mechanism description of high pressure NO formation chemistry using experiments and calculations for laminar lean premixed methane air flames, develop a statistical model of turbulence NO chemistry interactions using a Bunsen type jet flame, and utilize the high pressure chemistry and turbulence models in a commercial design code, then evaluate its predictions using data from an analog gas turbine combustor. Work to date has resulted in the following achievements: spatially resolved measurements of NO in high-pressure high-temperature flat flames, plus evaluation of the influence of flame radiation on the measured temperature profile; measurements of temperature and velocity PDFs for a turbulent methane/air flame were obtained for the first time, under operating conditions which allow their study in the distributed regimes, and the increase in EINO{sub x} with equivalence ratio predicted using a chemical kinetics model; and simulation of non-reacting combustor flow fields from ambient to elevated pressure and temperature conditions and comparison of those results with experimental velocity profiles.

  12. Measurements of turbulent premixed flame dynamics using cinema stereoscopic PIV

    NASA Astrophysics Data System (ADS)

    Steinberg, Adam M.; Driscoll, James F.; Ceccio, Steven L.

    2008-06-01

    A new experimental method is described that provides high-speed movies of turbulent premixed flame wrinkling dynamics and the associated vorticity fields. This method employs cinema stereoscopic particle image velocimetry and has been applied to a turbulent slot Bunsen flame. Three-component velocity fields were measured with high temporal and spatial resolutions of 0.9 ms and 140 μm, respectively. The flame-front location was determined using a new multi-step method based on particle image gradients, which is described. Comparisons are made between flame fronts found with this method and simultaneous CH-PLIF images. These show that the flame contour determined corresponds well to the true location of maximum gas density gradient. Time histories of typical eddy-flame interactions are reported and several important phenomena identified. Outwardly rotating eddy pairs wrinkle the flame and are attenuated at they pass through the flamelet. Significant flame-generated vorticity is produced downstream of the wrinkled tip. Similar wrinkles are caused by larger groups of outwardly rotating eddies. Inwardly rotating pairs cause significant convex wrinkles that grow as the flame propagates. These wrinkles encounter other eddies that alter their behavior. The effects of the hydrodynamic and diffusive instabilities are observed and found to be significant contributors to the formation and propagation of wrinkles.

  13. Blowoff dynamics of bluff body stabilized turbulent premixed flames

    SciTech Connect

    Chaudhuri, Swetaprovo; Kostka, Stanislav; Renfro, Michael W.; Cetegen, Baki M.

    2010-04-15

    This article concerns the flame dynamics of a bluff body stabilized turbulent premixed flame as it approaches lean blowoff. Time resolved chemiluminescence imaging along with simultaneous particle image velocimetry and OH planar laser-induced fluorescence were utilized in an axisymmetric bluff body stabilized, propane-air flame to determine the sequence of events leading to blowoff and provide a quantitative analysis of the experimental results. It was found that as lean blowoff is approached by reduction of equivalence ratio, flame speed decreases and the flame shape progressively changes from a conical to a columnar shape. For a stably burning conical flame away from blowoff, the flame front envelopes the shear layer vortices. Near blowoff, the columnar flame front and shear layer vortices overlap to induce high local stretch rates that exceed the extinction stretch rates instantaneously and in the mean, resulting in local flame extinction along the shear layers. Following shear layer extinction, fresh reactants can pass through the shear layers to react within the recirculation zone with all other parts of the flame extinguished. This flame kernel within the recirculation zone may survive for a few milliseconds and can reignite the shear layers such that the entire flame is reestablished for a short period. This extinction and reignition event can happen several times before final blowoff which occurs when the flame kernel fails to reignite the shear layers and ultimately leads to total flame extinguishment. (author)

  14. Turbulent premixed flames on fractal-grid-generated turbulence

    NASA Astrophysics Data System (ADS)

    Soulopoulos, N.; Kerl, J.; Sponfeldner, T.; Beyrau, F.; Hardalupas, Y.; Taylor, A. M. K. P.; Vassilicos, J. C.

    2013-12-01

    A space-filling, low blockage fractal grid is used as a novel turbulence generator in a premixed turbulent flame stabilized by a rod. The study compares the flame behaviour with a fractal grid to the behaviour when a standard square mesh grid with the same effective mesh size and solidity as the fractal grid is used. The isothermal gas flow turbulence characteristics, including mean flow velocity and rms of velocity fluctuations and Taylor length, were evaluated from hot-wire measurements. The behaviour of the flames was assessed with direct chemiluminescence emission from the flame and high-speed OH-laser-induced fluorescence. The characteristics of the two flames are considered in terms of turbulent flame thickness, local flame curvature and turbulent flame speed. It is found that, for the same flow rate and stoichiometry and at the same distance downstream of the location of the grid, fractal-grid-generated turbulence leads to a more turbulent flame with enhanced burning rate and increased flame surface area.

  15. A model of particle nucleation in premixed ethylene flames

    SciTech Connect

    D'Anna, Andrea; Sirignano, Mariano; Kent, John

    2010-11-15

    A detailed model of particle inception is proposed to delve into the physical structure and chemistry of combustion-formed particles. A sectional method is used, from a previously developed kinetic mechanism of particle formation with a double discretization of the particle phase in terms of C and H atom number. The present model also distinguishes between different particle structures based on their state of aggregation; single high molecular mass molecules, cluster of molecules and aggregates of clusters. The model predicts the mass of particles, hydrogen content and internal structure. It represents a first approach in following the chemical evolution and internal structure of the particles formed in flames, coupled with the main pyrolysis and oxidation of the fuel. The model is tested in atmospheric premixed flat flames of ethylene and the effect of fuel equivalence ratio on particle morphology is analyzed. Molecular weight growth of aromatic compounds and the inception of particles are predicted. The morphology of the particles and the number of molecules in the clusters at particle inception are also indicated. (author)

  16. Numerical simulation of premixed flame propagation in a closed tube

    NASA Astrophysics Data System (ADS)

    Kuzuu, Kazuto; Ishii, Katsuya; Kuwahara, Kunio

    1996-08-01

    Premixed flame propagation of methane-air mixture in a closed tube is estimated through a direct numerical simulation of the three-dimensional unsteady Navier-Stokes equations coupled with chemical reaction. In order to deal with a combusting flow, an extended version of the MAC method, which can be applied to a compressible flow with strong density variation, is employed as a numerical method. The chemical reaction is assumed to be an irreversible single step reaction between methane and oxygen. The chemical species are CH 4, O 2, N 2, CO 2, and H 2O. In this simulation, we reproduce a formation of a tulip flame in a closed tube during the flame propagation. Furthermore we estimate not only a two-dimensional shape but also a three-dimensional structure of the flame and flame-induced vortices, which cannot be observed in the experiments. The agreement between the calculated results and the experimental data is satisfactory, and we compare the phenomenon near the side wall with the one in the corner of the tube.

  17. Direct simulations of premixed turbulent flames with nonunity Lewis numbers

    NASA Technical Reports Server (NTRS)

    Rutland, C. J.; Trouve, A.

    1993-01-01

    A principal effect of turbulence on premixed flames in the flamelet regime is to wrinkle the flame fronts. For nonunity Lewis numbers, Le is not equal to 1, the local flame structure is altered in curved regions. This effect is examined using direct numerical simulations of 3D isotropic turbulence with constant density, single-step Arrhenius kinetics chemistry. Simulations of Lewis numbers 0.8, 1.0, and 1.2 are compared. At the local level, curvature effects dominated changes to the flame structure while strain effects were insignificant. A strong Lewis-number-dependent correlation was found between surface curvature and the local flame speed. The correlation was positive for Le less than 1 and negative for Le greater than 1. At the global level, strain-related effects were more significant than curvature effects. The turbulent flame speed changed significantly with Lewis number, increasing as Le decreased. This was found to be due to strain effects that have a nonzero mean over the flame surface, rather than to curvature effects that have a nearly zero mean. The mean product temperature was also found to vary with Lewis number, being higher for Le greater than 1 and lower for Le less than 1.

  18. Spatial resolution effects of CARS in turbulent premixed combustion thermometry

    SciTech Connect

    Shepherd, I.G. . Applied Science Div.); Porter, F.M.; Greenhalgh, D.A. )

    1990-10-01

    Coherent Anti-Stokes Raman Scattering CARS nitrogen thermometry has proved to be a successful technique to obtain point temperature measurements with high temporal resolution in hot reactive gases. It has significant advantages over other probe methods, such as thermocouples, where access, physical and/or chemical perturbation and a lack of sufficient temperature range may create problems. The longitudinal or axial resolution of a CARS measurement, in the preferred BOXCARS geometry, is determined by the zone of perfect overlap of the intersecting laser beams (typically 1-5 mm). The length squared dependence of the CARS signal, however, can limit the spatial resolution if usable signal-to-noise rations are to be obtained. This can be a particular problem when probing systems where steep temperature gradients exist. In this numerical study of a premixed turbulent flame zone the effect of spatial resolution on CARS temperature probability density functions (pdfs) and mean temperature profile measurements is assessed, and possible means to overcome this problem are presented.

  19. Spectral output from a premixed chain reaction cw HF laser

    SciTech Connect

    Stanton, A.C.; Bien, F.

    1980-07-01

    Spectral measurements of the output from a purely chemical chain reaction cw HF laser are reported. The laser is a subsonic H/sub 2/-F/sub 2/ flame, with supersonic premixing and spatially uniform initiation by a stationary normal shock. Initial chemical production of fluorine atoms is by the bimolecular reaction of F/sub 2/ with NO. Spectral measurements of the laser output near the initiating shock indicate lasing transitions in the P branches of the v=3 ..-->.. v=2, v=2 ..-->.. v=1, and v=1 ..-->.. v=0 HF bands. Further downstream, the upper vibrational levels are strongly deactivated, and lasing occurs only in the v=1 ..-->.. v=0 band. Laser emission in the v=2 ..-->.. v=1 band reappears at reduced NO flow rates, suggesting efficient deactivation of HF (v) by NO, possibly through multiquantum V-V exchange. An approximate rate of 5 x 10/sup -13plus-or-minus0.5/ cm/sup 3//sec for deactivation of HF (v=2) by NO is inferred.

  20. Stationary premixed flames in spherical and cylindrical geometries

    NASA Technical Reports Server (NTRS)

    Ronney, P. D.; Whaling, K. N.; Abbud-Madrid, A.; Gatto, J. L.; Pisowiscz, V. L.

    1994-01-01

    Stationary source-free spherical flames ('flame balls') in premixed combustible gases were studied by employing low-gravity (micro-g) environments in a drop tower and an aircraft flying parabolic trajectories to diminish the impact of buoyancy-induced convective flow. Flame balls were found in all mixture families tested when: (1) the Lewis number Le of the deficient reactant was sufficiently low; and (2) the compositions were sufficiently close to the flammability limits. Probably as a consequence of the reduction in buoyant convection, the flammability limits at micro-g were significantly more dilute than those at Earth gravity; for example, 3.35% H2 vs 4.0% H2 in lean H2-air mixtures. By comparison with analytical and computational models, it is inferred that the phenomenon is probably related to diffusive-thermal effects in low-Le mixtures in conjunction with flame-front curvature and radiative heat losses from the combustion products. The chemical reaction mechanism appears to play no qualitative role. In the aircraft experiments, the gravity levels (approximately equal 10(exp -2)g(sub 0)) were found to cause noticeable motion of flame balls due to buoyancy, which in turn influenced the behavior of flame balls. At these g levels, a new type of transient, nearly cylindrical flame structure, termed 'flame strings,' was observed.

  1. NASA/ESMD Analogue Mission Plans

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  2. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics.

    PubMed

    Pozzilli, Paolo; Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz-Chobot, Przemyslawa; Renard, Eric

    2016-01-01

    The level of glycaemic control necessary to achieve optimal short-term and long-term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid-acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health-related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid-acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost-effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid-acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin infusion on patients

  3. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics

    PubMed Central

    Battelino, Tadej; Danne, Thomas; Hovorka, Roman; Jarosz‐Chobot, Przemyslawa; Renard, Eric

    2015-01-01

    Summary The level of glycaemic control necessary to achieve optimal short‐term and long‐term outcomes in subjects with type 1 diabetes mellitus (T1DM) typically requires intensified insulin therapy using multiple daily injections or continuous subcutaneous insulin infusion. For continuous subcutaneous insulin infusion, the insulins of choice are the rapid‐acting insulin analogues, insulin aspart, insulin lispro and insulin glulisine. The advantages of continuous subcutaneous insulin infusion over multiple daily injections in adult and paediatric populations with T1DM include superior glycaemic control, lower insulin requirements and better health‐related quality of life/patient satisfaction. An association between continuous subcutaneous insulin infusion and reduced hypoglycaemic risk is more consistent in children/adolescents than in adults. The use of continuous subcutaneous insulin infusion is widely recommended in both adult and paediatric T1DM populations but is limited in pregnant patients and those with type 2 diabetes mellitus. All available rapid‐acting insulin analogues are approved for use in adult, paediatric and pregnant populations. However, minimum patient age varies (insulin lispro: no minimum; insulin aspart: ≥2 years; insulin glulisine: ≥6 years) and experience in pregnancy ranges from extensive (insulin aspart, insulin lispro) to limited (insulin glulisine). Although more expensive than multiple daily injections, continuous subcutaneous insulin infusion is cost‐effective in selected patient groups. This comprehensive review focuses on the European situation and summarises evidence for the efficacy and safety of continuous subcutaneous insulin infusion, particularly when used with rapid‐acting insulin analogues, in adult, paediatric and pregnant populations. The review also discusses relevant European guidelines; reviews issues that surround use of this technology; summarises the effects of continuous subcutaneous insulin

  4. Photon-counting chirped amplitude modulation lidar using a smart premixing method.

    PubMed

    Zhang, Zijing; Zhang, Jianlong; Wu, Long; Zhang, Yong; Zhao, Yuan; Su, Jianzhong

    2013-11-01

    We proposed a new premixing method for photon-counting chirped amplitude modulation lidar (PCCAML). Earlier studies used the counting results of the returned signal detected by a Geiger mode avalanche photodiode detector (Gm-APD) to mix with the reference signal, called the postmixing method. We use an alternative method known as the premixing method, in which the reference signal is used to directly modulate the sampling gate width of the Gm-APD, and the mixing of the returned signal and the reference signal is completed before the Gm-APD. This premixing method is more flexible and may perform better than the postmixing method in terms of signal-to-noise ratio by cutting down a separated mixer commonly used in the postmixing lidar system. Furthermore, this premixing method lowers the demand for the sampling frequency of the Gm-APD. It allows the use of a much wider modulation bandwidth to improve the range accuracy and resolution. To the best of our knowledge, this is the first report to use the premixing method in the PCCAML system, which will benefit future lidar applications.

  5. Intrauterine-like growth rates can be achieved with premixed parenteral nutrition solution in preterm infants.

    PubMed

    Rigo, Jacques; Senterre, Thibault

    2013-12-01

    Growth failure in neonatal intensive care units is a major challenge for pediatricians and neonatologists. The use of early "aggressive" parenteral nutrition (PN), with >2.5 g/(kg ·d) of amino acids and at least 40 kcal/(kg ·d) of energy from the first day of life, has been shown to provide nutritional intakes in the range recommended by international guidelines, reducing nutritional deficit and the incidence of postnatal growth restriction in preterm infants. However, nutritional practices and adherence to recommendations may vary in different hospitals. Two ready-to-use (RTU), premixed parenteral solutions (PSs) designed for preterm infants have been prospectively evaluated: a binary RTU premixed PS from our hospital pharmacy and a commercially premixed 3-chamber bag (Baxter Healthcare). These premixed PSs provide nitrogen and energy intakes in the range of the most recent recommendations, reducing or eliminating the early cumulative nutritional deficit in very-low-birth-weight infants, and avoiding the development of postnatal growth restriction. A further rationale for RTU premixed PSs is that preterm infants require balanced PN that contains not only amino acids and energy but also minerals and electrolytes from the first day of life in order to reduce the incidence of metabolic disorders frequently reported in extremely-low-birth-weight infants during the early weeks of life.

  6. Swozzle based burner tube premixer including inlet air conditioner for low emissions combustion

    DOEpatents

    Tuthill, Richard Sterling; Bechtel, II, William Theodore; Benoit, Jeffrey Arthur; Black, Stephen Hugh; Bland, Robert James; DeLeonardo, Guy Wayne; Meyer, Stefan Martin; Taura, Joseph Charles; Battaglioli, John Luigi

    2002-01-01

    A burner for use in a combustion system of a heavy-duty industrial gas turbine includes a fuel/air premixer having an air inlet, a fuel inlet, and an annular mixing passage. The fuel/air premixer mixes fuel and air into a uniform mixture for injection into a combustor reaction zone. The burner also includes an inlet flow conditioner disposed at the air inlet of the fuel/air premixer for controlling a radial and circumferential distribution of incoming air. The pattern of perforations in the inlet flow conditioner is designed such that a uniform air flow distribution is produced at the swirler inlet annulus in both the radial and circumference directions. The premixer includes a swozzle assembly having a series of preferably air foil shaped turning vanes that impart swirl to the airflow entering via the inlet flow conditioner. Each air foil contains internal fuel flow passages that introduce natural gas fuel into the air stream via fuel metering holes that pass through the walls of the air foil shaped turning vanes. By injecting fuel in this manner, an aerodynamically clean flow field is maintained throughout the premixer. By injecting fuel via two separate passages, the fuel/air mixture strength distribution can be controlled in the radial direction to obtain optimum radial concentration profiles for control of emissions, lean blow outs, and combustion driven dynamic pressure activity as machine and combustor load are varied.

  7. Decision analysis applied to the purchase of frozen premixed intravenous admixtures.

    PubMed

    Witte, K W; Eck, T A; Vogel, D P

    1985-04-01

    A structured decision-analysis model was used to evaluate frozen premixed cefazolin admixtures. Decision analysis is a process of stating the desired outcome, establishing and weighting evaluation criteria, identifying options for reaching the outcome, evaluating and numerically ranking each option for each criterion, multiplying the ranking by the weight for each criterion, and calculating total points for each option. It was used to compare objectively frozen premixed cefazolin admixtures with batch reconstitution from vials and reconstitution of lyophilized, ready-to-mix containers. In this institution the model numerically demonstrated a distinct preference for the premixed frozen admixture over these other alternatives. A comparison of these results with the total cost impact of each option resulted in a decision to purchase the frozen premixed solution. The advantages of the frozen premixed solution that contributed most to this decision were decreased waste and personnel time. The latter was especially important since it allowed for the reallocation of personnel resources to other potentially cost-reducing clinical functions. Decision analysis proved to be an effective tool for formalizing the process of selecting among various alternatives to reach a desired outcome in this hospital pharmacy.

  8. A Novel Insulin Secretagogue Based on a Dinucleoside Polyphosphate Scaffold

    PubMed Central

    Eliahu, Shay; Barr, Haim M.; Camden, Jean; Weisman, Gary A.; Fischer, Bilha

    2015-01-01

    Dinucleoside polyphosphates exert their physiological effects via P2 receptors (P2Rs). They are attractive drug candidates, as they offer better stability and specificity compared to nucleotides, the most common P2 receptor ligands. The activation of pancreatic P2Y receptors by nucleotides increases insulin secretion. Therefore, in the current study, dinucleoside polyphosphate analogues (di-(2-MeS)-adenosine-5′,5″-P1,P4,α,β-methylene-tetraphosphate), 8, (di-(2-MeS)-adenosine-5′,5″-P1,P4,β,γ-methylene-tetraphosphate), 9, and di-(2-MeS)-adenosine-5′,5″-P1,P3,α,β-methylene triphosphate, 10, were developed as potential insulin secretagogues. Analogues 8 and 9 were found to be agonists of the P2Y1R with EC50 values of 0.42 and 0.46 μM, respectively, whereas analogue 10 had no activity. Analogues 8–10 were found to be completely resistant to hydrolysis by alkaline phosphatase over 3 h at 37°C. Analogue 8 also was found to be 2.5-fold more stable in human blood serum than ATP, with a half-life of 12.1 h. Analogue 8 administration in rats caused a decrease in a blood glucose load from 155 mg/dL to ca. 100 mg/dL and increased blood insulin levels 4-fold as compared to basal levels. In addition, analogue 8 reduced a blood glucose load to normal values (80–110 mg/dL), unlike the commonly prescribed glibenclamide, which reduced glucose levels below normal values (60 mg/dL). These findings suggest that analogue 8 may prove to be an effective and safe treatment for type 2 diabetes. PMID:20175517

  9. [Cloning, expressing of exendin-4 analogue and bioactivity analysis in vivo].

    PubMed

    Li, Taiming; Gu, Chunjiao; Ge, Xiaoyu; Li, Zhezhe; Wang, Dan; Ma, Yanhong; Liu, Tao; Zhang, Meiyou; Li, Li; Liu, Jingjing

    2012-07-01

    To construct, express and purify Exendin-4 analogue and detect its biological activity in vivo. Insert gene sequence into fusion partner ofpED plasmid which is helped to purification, entitled the new recombinant plasmid 5 Exendin-4 analogue polypeptide gene and fusion partner gene was linked by acid hydrolysisgene, transformed to E. coli BL21 and the fusion protein was induced by lactose. After acid hydrolysis, the Exendin-4 analogue polypeptide separated from fusion chaperon. Anion charge chromatography were used to further purification. 6 to 8 week-old ICR mice were injected (s.c) with Exendin-4 analogue, blood glucose and plasma insulin level was detected in different period after oral glucose tolerance test. The results show that high expression of inclusion body was induced by lactose, which accounted for 40% of germ proteins, the Exendin-4 analogue was obtained with the purity of 91.8% after being purified by anion charge chromatography. Bioactivity assay showed that the level of blood glucose of mouse which treated with exendin-4 analogue was obviously decreased to normal (P < 0.01), and the level of plasma insulin was increased obviously (P < 0.01).

  10. Enhanced Laser System for Two-Point Scalar Time-Series Measurements in Turbulent Partially Premixed Flames

    DTIC Science & Technology

    2007-05-15

    combustion systems of interest to the Air Force to be studied including thermoacoustic instabilities and partially premixed turbulent combustion. 15...SUBJECT TERMS Laser diagnostics, turbulent combustion, thermoacoustic instabilities, partially premixed combustion 16. SECURITY CLASSIFICATION OF... thermoacoustic instabilities in a Rijke combustor. TECHNICAL DISCUSSION Two-point time-series measurements of OH have been obtained in four turbulent

  11. Cellular Cations Control Conformational Switching of Inositol Pyrophosphate Analogues.

    PubMed

    Hager, Anastasia; Wu, Mingxuan; Wang, Huanchen; Brown, Nathaniel W; Shears, Stephen B; Veiga, Nicolás; Fiedler, Dorothea

    2016-08-22

    The inositol pyrophosphate messengers (PP-InsPs) are emerging as an important class of cellular regulators. These molecules have been linked to numerous biological processes, including insulin secretion and cancer cell migration, but how they trigger such a wide range of cellular responses has remained unanswered in many cases. Here, we show that the PP-InsPs exhibit complex speciation behaviour and propose that a unique conformational switching mechanism could contribute to their multifunctional effects. We synthesised non-hydrolysable bisphosphonate analogues and crystallised the analogues in complex with mammalian PPIP5K2 kinase. Subsequently, the bisphosphonate analogues were used to investigate the protonation sequence, metal-coordination properties, and conformation in solution. Remarkably, the presence of potassium and magnesium ions enabled the analogues to adopt two different conformations near physiological pH. Understanding how the intrinsic chemical properties of the PP-InsPs can contribute to their complex signalling outputs will be essential to elucidate their regulatory functions.

  12. Which insulin, regimen and device in type 2 diabetes?

    PubMed

    2010-12-01

    Around 4% of the UK population have diabetes mellitus.1 Around 90% have type 2 disease and many of these people will need insulin therapy for effective control of their diabetes. The different types of insulin (animal, human or analogue), regimen (timing of doses and duration of action of insulin) and device (syringes, prefilled or disposable pens) present various advantages and disadvantages that can affect adherence, quality of life and glycaemic control.2 Here we provide an overview of the various treatment options available, and offer practical advice on how to choose the appropriate approach for adults with type 2 diabetes.

  13. Challenges constraining access to insulin in the private-sector market of Delhi, India.

    PubMed

    Sharma, Abhishek; Kaplan, Warren A

    2016-01-01

    India's majority of patients-including those living with diabetes-seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative interviews with insulin retailers (pharmacists) and wholesalers to understand insulin market dynamics. In 40 pharmacy outlets analysed, mean availability of the human and analogue insulins on the 2013 Delhi essential medicine list was 44.4% and 13.1%, respectively. 82% of pharmacies had domestically manufactured human insulin phials, primarily was made in India under licence to overseas pharmaceutical companies. Analogue insulin was only in cartridge and pen forms that were 4.42 and 5.81 times, respectively, the price of human insulin phials. Domestically manufactured human phial and cartridge insulin (produced for foreign and Indian companies) was less expensive than their imported counterparts. The lowest paid unskilled government worker in Delhi would work about 1.5 and 8.6 days, respectively, to be able to pay OOP for a monthly supply of human phial and analogue cartridge insulin. Interviews suggest that the Delhi insulin market is dominated by a few multinational companies that import and/or license in-country production. Several factors influence insulin uptake by patients, including doctor's prescribing preference. Wholesalers have negative perceptions about domestic insulin manufacturing. The Delhi insulin market is an oligopoly with limited market competition. Increasing competition from Indian companies is going to require some additional policies, not presently in place. As more Indian companies produce biosimilars, brand substitution policies are needed to be able to benefit from market competition.

  14. Challenges constraining access to insulin in the private-sector market of Delhi, India

    PubMed Central

    Kaplan, Warren A

    2016-01-01

    Objective India's majority of patients—including those living with diabetes—seek healthcare in the private sector through out-of-pocket (OOP) payments. We studied access to insulin in the private-sector market of Delhi state, India. Methods A modified World Health Organization/Health Action International (WHO/HAI) standard survey to assess insulin availability and prices, and qualitative interviews with insulin retailers (pharmacists) and wholesalers to understand insulin market dynamics. Results In 40 pharmacy outlets analysed, mean availability of the human and analogue insulins on the 2013 Delhi essential medicine list was 44.4% and 13.1%, respectively. 82% of pharmacies had domestically manufactured human insulin phials, primarily was made in India under licence to overseas pharmaceutical companies. Analogue insulin was only in cartridge and pen forms that were 4.42 and 5.81 times, respectively, the price of human insulin phials. Domestically manufactured human phial and cartridge insulin (produced for foreign and Indian companies) was less expensive than their imported counterparts. The lowest paid unskilled government worker in Delhi would work about 1.5 and 8.6 days, respectively, to be able to pay OOP for a monthly supply of human phial and analogue cartridge insulin. Interviews suggest that the Delhi insulin market is dominated by a few multinational companies that import and/or license in-country production. Several factors influence insulin uptake by patients, including doctor's prescribing preference. Wholesalers have negative perceptions about domestic insulin manufacturing. Conclusions The Delhi insulin market is an oligopoly with limited market competition. Increasing competition from Indian companies is going to require some additional policies, not presently in place. As more Indian companies produce biosimilars, brand substitution policies are needed to be able to benefit from market competition. PMID:28588966

  15. Vortex combustor for low NOx emissions when burning lean premixed high hydrogen content fuel

    SciTech Connect

    Steele, Robert C; Edmonds, Ryan G; Williams, Joseph T; Baldwin, Stephen P

    2009-10-20

    A trapped vortex combustor. The trapped vortex combustor is configured for receiving a lean premixed gaseous fuel and oxidant stream, where the fuel includes hydrogen gas. The trapped vortex combustor is configured to receive the lean premixed fuel and oxidant stream at a velocity which significantly exceeds combustion flame speed in a selected lean premixed fuel and oxidant mixture. The combustor is configured to operate at relatively high bulk fluid velocities while maintaining stable combustion, and low NOx emissions. The combustor is useful in gas turbines in a process of burning synfuels, as it offers the opportunity to avoid use of diluent gas to reduce combustion temperatures. The combustor also offers the possibility of avoiding the use of selected catalytic reaction units for removal of oxides of nitrogen from combustion gases exiting a gas turbine.

  16. Vortex combustor for low NOX emissions when burning lean premixed high hydrogen content fuel

    SciTech Connect

    Steele, Robert C; Edmonds, Ryan G; Williams, Joseph T; Baldwin, Stephen P

    2012-11-20

    A trapped vortex combustor. The trapped vortex combustor is configured for receiving a lean premixed gaseous fuel and oxidant stream, where the fuel includes hydrogen gas. The trapped vortex combustor is configured to receive the lean premixed fuel and oxidant stream at a velocity which significantly exceeds combustion flame speed in a selected lean premixed fuel and oxidant mixture. The combustor is configured to operate at relatively high bulk fluid velocities while maintaining stable combustion, and low NOx emissions. The combustor is useful in gas turbines in a process of burning synfuels, as it offers the opportunity to avoid use of diluent gas to reduce combustion temperatures. The combustor also offers the possibility of avoiding the use of selected catalytic reaction units for removal of oxides of nitrogen from combustion gases exiting a gas turbine.

  17. Exhaust emissions from a premixing, prevaporizing flame tube using liquid jet A fuel

    NASA Technical Reports Server (NTRS)

    Marek, C. J.; Papathakos, L. C.

    1976-01-01

    Emissions of nitrogen oxides, carbon monoxide, and unburned hydrocarbons were measured in a burner where liquid Jet A fuel was sprayed into the heated air stream and vaporized upstream of a perforated plate flameholder. The burner was tested at inlet air temperatures at 640, 800, and 833 K, an inlet pressure of 5.6 X 100,000 N/m squared, a reference velocity of 25 m/sec, and equivalence ratios from lean blowout to 0.7. Nitrogen oxide levels of below 1.0 g NO2/kg fuel were obtained at combustion efficiencies greater than 99 percent. The measured emission levels for the liquid fuel agreed well with previously reported premixed gaseous propane data and agreed with well stirred reactor predictions. Autoignition of the premixed fuel air mixture was a problem at inlet temperatures above 650 K with 104 msec premixing time.

  18. Effect of premixing quality on oxides of nitrogen in gas turbine combustors foi HC

    NASA Technical Reports Server (NTRS)

    Roffe, G.; Ferri, A.

    1976-01-01

    Experiments were conducted to determine the effectiveness of several premixing prevaporizing gas turbine combustor designs in reducing formation of oxides of nitrogen at the supersonic cruise condition. An atomized spray from a single injector mounted on the axis of the mixer tube produced a high initial concentration of fuel near the axis and only moderate premixed conditions entering the combustor. A fuel spray produced by 12 flush-mounted normal injection orifices in the mixer tube wall produced a good initial despersion of fuel and resulted in nearly complete premixing. Oxides of nitrogen emission levels of the order of 0.2 g NO2/kg fuel were obtained at 99 percent combustion efficiency at an equivalence ratio of 0.4. Overall total pressure drop was less than 3 percent through the 1-meter combustor module.

  19. PREMIX: PRivacy-preserving EstiMation of Individual admiXture.

    PubMed

    Chen, Feng; Dow, Michelle; Ding, Sijie; Lu, Yao; Jiang, Xiaoqian; Tang, Hua; Wang, Shuang

    2016-01-01

    In this paper we proposed a framework: PRivacy-preserving EstiMation of Individual admiXture (PREMIX) using Intel software guard extensions (SGX). SGX is a suite of software and hardware architectures to enable efficient and secure computation over confidential data. PREMIX enables multiple sites to securely collaborate on estimating individual admixture within a secure enclave inside Intel SGX. We implemented a feature selection module to identify most discriminative Single Nucleotide Polymorphism (SNP) based on informativeness and an Expectation Maximization (EM)-based Maximum Likelihood estimator to identify the individual admixture. Experimental results based on both simulation and 1000 genome data demonstrated the efficiency and accuracy of the proposed framework. PREMIX ensures a high level of security as all operations on sensitive genomic data are conducted within a secure enclave using SGX.

  20. PREMIX: PRivacy-preserving EstiMation of Individual admiXture

    PubMed Central

    Chen, Feng; Dow, Michelle; Ding, Sijie; Lu, Yao; Jiang, Xiaoqian; Tang, Hua; Wang, Shuang

    2016-01-01

    In this paper we proposed a framework: PRivacy-preserving EstiMation of Individual admiXture (PREMIX) using Intel software guard extensions (SGX). SGX is a suite of software and hardware architectures to enable efficient and secure computation over confidential data. PREMIX enables multiple sites to securely collaborate on estimating individual admixture within a secure enclave inside Intel SGX. We implemented a feature selection module to identify most discriminative Single Nucleotide Polymorphism (SNP) based on informativeness and an Expectation Maximization (EM)-based Maximum Likelihood estimator to identify the individual admixture. Experimental results based on both simulation and 1000 genome data demonstrated the efficiency and accuracy of the proposed framework. PREMIX ensures a high level of security as all operations on sensitive genomic data are conducted within a secure enclave using SGX. PMID:28269933

  1. Study of premixing phase of steam explosion with JASMINE code in ALPHA program

    SciTech Connect

    Moriyama, Kiyofumi; Yamano, Norihiro; Maruyama, Yu; Kudo, Tamotsu; Sugimoto, Jun

    1996-08-01

    Premixing phase of steam explosion has been studied in ALPHA Program at Japan Atomic Energy Research Institute (JAERI). An analytical model to simulate the premixing phase, JASMINE (JAERI Simulator for Multiphase Interaction and Explosion), has been developed based on a multi-dimensional multi-phase thermal hydraulics code MISTRAL (by Fuji Research Institute Co.). The original code was extended to simulate the physics in the premixing phenomena. The first stage of the code validation was performed by analyzing two mixing experiments with solid particles and water: the isothermal experiment by Gilbertson et al. (1992) and the hot particle experiment by Angelini et al. (1993) (MAGICO). The code predicted reasonably well the experiments. Effectiveness of the TVD scheme employed in the code was also demonstrated.

  2. An Investigation of a Hybrid Mixing Timescale Model for PDF Simulations of Turbulent Premixed Flames

    NASA Astrophysics Data System (ADS)

    Zhou, Hua; Kuron, Mike; Ren, Zhuyin; Lu, Tianfeng; Chen, Jacqueline H.

    2016-11-01

    Transported probability density function (TPDF) method features the generality for all combustion regimes, which is attractive for turbulent combustion simulations. However, the modeling of micromixing due to molecular diffusion is still considered to be a primary challenge for TPDF method, especially in turbulent premixed flames. Recently, a hybrid mixing rate model for TPDF simulations of turbulent premixed flames has been proposed, which recovers the correct mixing rates in the limits of flamelet regime and broken reaction zone regime while at the same time aims to properly account for the transition in between. In this work, this model is employed in TPDF simulations of turbulent premixed methane-air slot burner flames. The model performance is assessed by comparing the results from both direct numerical simulation (DNS) and conventional constant mechanical-to-scalar mixing rate model. This work is Granted by NSFC 51476087 and 91441202.

  3. Spatially resolved laser-induced breakdown spectroscopy in laminar premixed methane-air flames

    NASA Astrophysics Data System (ADS)

    Tian, Zhaohua; Dong, Meirong; Li, Shishi; Lu, Jidong

    2017-10-01

    Laser-induced breakdown spectroscopy was evaluated for the analysis of the structure of laminar premixed methane-air flames. Firstly, breakdown threshold pulse energy and plasma energy in different areas of the flame were measured simultaneously, and an approximate linear relation between them was detected. Secondly, a new approach was proposed to qualitatively characterize the flame temperature distributions based on the plasma energy distributions. Finally, combination of the spatial analysis of the spectrum intensity, plasma energy and equivalence ratio, the laminar premixed flames structure was investigated deeply, including the distribution of the flame temperature, the width and distribution of different flame region (e.g. premixed combustion regions, high temperature regions.),as well as the location of the flame front.

  4. Gravitational Influences on Flame Propagation Through Non-Uniform Premixed Gas Systems

    NASA Technical Reports Server (NTRS)

    Miller, Fletcher J.; Easton, John; Ross, Howard D.; Marchese, Anthony

    1999-01-01

    Flame propagation through non-uniformly premixed gases occurs in several common combustion situations. As summarized in a previous conference paper, non-uniform premixed gas combustion has received scant attention compared to the more usual limiting cases of diffusion or uniformly premixed flames. It is the goal of this research to further our knowledge of layered combustion, in which a fuel concentration gradient exists normal to the direction of flame spread, in particular by focusing on the role that gravity plays. Gravity can affect flame propagation in at least three ways: through a hydrostatic pressure gradient, by altering the initial distribution of fuel vapor, and through buoyantly induced flows once ignition has occurred. An understanding of the phenomena involved is important to fire safety, especially aboard spacecraft since no microgravity data exist. The data obtained will also be useful to verify theoretical models of this problem, which are easier to implement if buoyancy is neglected.

  5. Therapeutics in pediatric diabetes: insulin and non-insulin approaches. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni.

    PubMed

    Kim, Jongoh; Kim, Se Min; Nguyen, Ha Cam Thuy; Redondo, Maria Jose

    2012-01-01

    Treatment of pediatric diabetes can be challenging. Strict glucose control can be accompanied by hypoglycemia and weight gain. Recently, there have been many developments in insulin preparations and delivery methods which make insulin levels more close to a physiologic pattern. Newly developed rapid/long acting analogues and delivery devices such as continuous subcutaneous insulin infusion (CSII, insulin pump) may reduce hypoglycemia and improve glycemic control. CSII combined with continuous glucose monitoring can achieve even better glycemic control. The closed-loop system is rapidly evolving and an artificial pancreas will be available in the near future. It is now recognized that several hormones other than insulin such as glucagon, amylin, and incretins contribute to glucose homeostasis. The role of co-adjuncts such as metformin, amylin analogues, and incretin based therapy is now emerging. Immunotherapy in a high risk population or patients in the early phase of type 1 diabetes may prevent further destruction of pancreatic β cells.

  6. A new piloted premixed jet burner to study strong finite-rate chemistry effects

    SciTech Connect

    Dunn, Matthew J.; Masri, Assaad R.; Bilger, Robert W.

    2007-10-15

    This paper describes the initial characterization of a piloted premixed jet burner (PPJB) designed to investigate finite-rate chemistry effects in highly turbulent lean premixed combustion. The PPJB consists of a high-velocity lean premixed central jet, piloted by a low-velocity stoichiometric premixed pilot, surrounded by a large-diameter coflow of lean premixed hydrogen-air combustion products. The configuration of a lean central jet supported by a stoichiometric pilot is similar to that of a lean premixed gas turbine combustor, but without additional complications such as swirl, recirculation, and complex boundary conditions. A significant feature of the PPJB is that under certain conditions the central jet combustion process appears to undergo an extinction-reignition process. It is considered likely that intense turbulent mixing after the nozzle drives an initial extinction process that reduces flame luminosity, with reignition occurring downstream where turbulent mixing has decreased, causing an increase in flame luminosity. Four flames are selected for further study, each with an equivalence ratio of 0.5 and with central jet velocities of 50, 100, 150, and 200 m/s. Simultaneous two-dimensional (2D) Rayleigh-OH planar laser-induced fluorescence (PLIF) imaging results are presented for the selected flames, showing that in the ''extinction'' region OH concentrations occur at reduced levels in isolated patchy regions, supporting the idea that extinction is predominantly occurring. Laser Doppler velocimetry (LDV) data are also reported for the flow field turbulence statistics, with the most significant result being that for the reacting cases the pilot delays the occurrence of peak turbulence intensity downstream to near the observed ''extinction'' region. (author)

  7. Tabulated Combustion Model Development For Non-Premixed Flames

    NASA Astrophysics Data System (ADS)

    Kundu, Prithwish

    Turbulent non-premixed flames play a very important role in the field of engineering ranging from power generation to propulsion. The coupling of fluid mechanics and complicated combustion chemistry of fuels pose a challenge for the numerical modeling of these type of problems. Combustion modeling in Computational Fluid Dynamics (CFD) is one of the most important tools used for predictive modeling of complex systems and to understand the basic fundamentals of combustion. Traditional combustion models solve a transport equation of each species with a source term. In order to resolve the complex chemistry accurately it is important to include a large number of species. However, the computational cost is generally proportional to the cube of number of species. The presence of a large number of species in a flame makes the use of CFD computationally expensive and beyond reach for some applications or inaccurate when solved with simplified chemistry. For highly turbulent flows, it also becomes important to incorporate the effects of turbulence chemistry interaction (TCI). The aim of this work is to develop high fidelity combustion models based on the flamelet concept and to significantly advance the existing capabilities. A thorough investigation of existing models (Finite-rate chemistry and Representative Interactive Flamelet (RIF)) and comparative study of combustion models was done initially on a constant volume combustion chamber with diesel fuel injection. The CFD modeling was validated with experimental results and was also successfully applied to a single cylinder diesel engine. The effect of number of flamelets on the RIF model and flamelet initialization strategies were studied. The RIF model with multiple flamelets is computationally expensive and a model was proposed on the frame work of RIF. The new model was based on tabulated chemistry and incorporated TCI effects. A multidimensional tabulated chemistry database generation code was developed based on the 1

  8. An Experimental Investigation of Premixed Combustion in Extreme Turbulence

    NASA Astrophysics Data System (ADS)

    Wabel, Timothy Michael

    This work has explored various aspects of high Reynolds number combustion that have received much previous speculation. A new high-Reynolds number premixed Bunsen burner, called Hi-Pilot, was designed to produce turbulence intensities in the extreme range of turbulence. The burner was modified several times in order to prevent boundary layer separation in the nozzle, and a large co-flow was designed that was capable of maintaining reactions over the entire flame surface. Velocity and turbulence characteristics were measured using a combination of Laser Doppler Velocimetry (LDV) and Particle Image Velocimetry (PIV). Flame structure was studied using a combination of formaldehyde (CH2O), hydroxyl (OH), and the CH radical. Planar Laser Induced Fluorescence (PLIF). The spatial Overlap of formaldehyde and OH PLIF qualitatively measures the reaction rate between formaldehyde molecules and OH radicals, and is a measure of the reaction layers of the flame. CH PLIF provides an alternative measure of the reaction zone, and was measured to compare with the Overlap PLIF results. Reaction layers are the full-width at half-maximum of the Overlap or CH PLIF signal, and extinction events were defined as regions where the PLIF signal drops below this threshold. Preheat structures were measured using formaldehyde PLIF, and are defined as beginning at 35% of the local maximum PLIF signal, and continue up to the leading edge of the reaction layer. Previous predictions of regime diagram boundaries were tested at the largest values of turbulent Reynolds number to date. The Overlap and CH PLIF diagnostics allowed extensive testing of the predicted broken reaction zones boundary of Peters. Measurements indicated that all run conditions are in the Broadened Preheat - Thin Reaction layers regime, but several conditions are expected to display a broken reaction zone structure. Therefore the work shows that Peters's predicted boundary is not correct, and therefore a Karlovitz number of 100 is

  9. Spatially resolved heat release rate measurements in turbulent premixed flames

    SciTech Connect

    Ayoola, B.O.; Kaminski, C.F.; Balachandran, R.; Mastorakos, E.; Frank, J.H.

    2006-01-01

    Heat release rate is a fundamental property of great importance for the theoretical and experimental elucidation of unsteady flame behaviors such as combustion noise, combustion instabilities, and pulsed combustion. Investigations of such thermoacoustic interactions require a reliable indicator of heat release rate capable of resolving spatial structures in turbulent flames. Traditionally, heat release rate has been estimated via OH or CH radical chemiluminescence; however, chemiluminescence suffers from being a line-of-sight technique with limited capability for resolving small-scale structures. In this paper, we report spatially resolved two-dimensional measurements of a quantity closely related to heat release rate. The diagnostic technique uses simultaneous OH and CH{sub 2}O planar laser-induced fluorescence (PLIF), and the pixel-by-pixel product of the OH and CH{sub 2}O PLIF signals has previously been shown to correlate well with local heat release rates. Results from this diagnostic technique, which we refer to as heat release rate imaging (HR imaging), are compared with traditional OH chemiluminescence measurements in several flames. Studies were performed in lean premixed ethylene flames stabilized between opposed jets and with a bluff body. Correlations between bulk strain rates and local heat release rates were obtained and the effects of curvature on heat release rate were investigated. The results show that the heat release rate tends to increase with increasing negative curvature for the flames investigated for which Lewis numbers are greater than unity. This correlation becomes more pronounced as the flame gets closer to global extinction.

  10. Lean premixed flames for low NO{sub x} combustors

    SciTech Connect

    Sojka, P.; Tseng, L.; Bryjak, J.

    1995-10-01

    Gas turbines are being used throughout the world to generate electricity. Due to increasing fuel costs and environmental concerns, gas turbines must meet stringent performance requirements, demonstrating high thermal efficiencies and low pollutant emissions. In order for U.S. manufactured gas turbines to stay competitive, their NO{sub x} levels must be below 10 ppm and their thermal efficiencies should approach 60%. Current technology is being stretched to achieve these goals. The twin goals of high efficiency and low NO{sub x} emissions require extending the operating range of current gas turbines. Higher efficiency requires operation at higher pressures and temperatures. Lower NO{sub x} emissions requires lower flame temperatures. Lower flame temperatures can be achieved through partially to fully pre-mixed combustion. However, increased performance and lower emissions result in a set of competing goals. In order to achieve a successful compromise between high efficiency and low NO{sub x} emissions, advanced design tools must be developed. One key design tool is a computationally efficient, high pressure, turbulent flow, combustion model capable of predicting pollutant formation in an actual gas turbine. Its development is the goal of this program. Achieving this goal requires completion of three tasks. The first task is to develop a reduced chemical kinetics model describing N{sub O}x formation in natural gas-air systems. The second task is to develop a computationally efficient model that describes turbulence-chemistry interactions. The third task is to incorporate the reduced chemical kinetics and turbulence-chemistry interaction models into a commercially available flow solver and compare its predictions with experimental data obtained under carefully controlled conditions so that the accuracy of model predictions can be evaluated.

  11. Premixed Flame-Vortex Interactions Imaged in Microgravity

    NASA Technical Reports Server (NTRS)

    Driscoll, J. F.; Sichel, M.; Sinibaldi, J. O.

    1997-01-01

    A unique experiment makes it now possible to obtain detailed images in microgravity showing how an individual vortex causes the wrinkling, stretching, area increase, and eventual extinction of a premixed flame. The repeatable, controllable flame-vortex interaction represents the fundamental building block of turbulent combustion concepts. New information is provided that is central to turbulent flame models, including measurements of all components of flame stretch, strain, and vorticity. Simultaneous measurements of all components of these quantities are not possible in fully turbulent flames but are possible in the present axisymmetric, repeatable experiment. Advanced PIV diagnostics have been used at one-g and have been developed for microgravity. Numerical simulations of the interaction are being performed at NRL. It is found that microgravity conditions greatly augment the flame wrinkling process. Flame area and the amplitude of wrinkles at zero-g are typically twice that observed at one-g. It is inferred that turbulent flames in microgravity could have larger surface area and thus propagate significantly faster than those in one-g, which is a potential safety hazard. A new mechanism is identified by PIV images that shows how buoyancy retards flame wrinkling at one-g; buoyancy produces new vorticity (due to baroclinic torques) that oppose the wrinkling and the stretch imposed by the original vortex. Microgravity conditions remove this stabilizing mechanism and the amplitude of flame wrinkling typically is found to double. Microgravity also increases the flame speed by a factor of 1.8 to 2.2. Both methane and propane-air flames were studied at the NASA Lewis drop tower. Results indicate that it is important to add buoyancy to models of turbulent flames to simulate the correct flame wrinkling, stretch and burning velocity.

  12. Characteristics of Non-Premixed Turbulent Flames in Microgravity

    NASA Technical Reports Server (NTRS)

    Hegde, U.; Yuan, Z. G.; Stocker, D. P.; Bahadori, M. Y.

    2001-01-01

    This project is concerned with the characteristics of turbulent hydrocarbon (primarily propane) gas-jet diffusion flames in microgravity. A microgravity environment provides the opportunity to study the structure of turbulent diffusion flames under momentum-dominated conditions (large Froude number) at moderate Reynolds number which is a combination not achievable in normal gravity. This paper summarizes progress made since the last workshop. Primarily, the features of flame radiation from microgravity turbulent jet diffusion flames in a reduced gravity environment are described. Tests were conducted for non-premixed, nitrogen diluted propane flames burning in quiescent air in the NASA Glenn 5.18 Second Zero Gravity Facility. Measured flame radiation from wedge-shaped, axial slices of the flame are compared for microgravity and normal gravity flames. Results from numerical computations of the flame using a k-e model for the turbulence are also presented to show the effects of flame radiation on the thermal field. Flame radiation is an important quantity that is impacted by buoyancy as has been shown in previous studies by the authors and also by Urban et al. It was found that jet diffusion flames burning under microgravity conditions have significantly higher radiative loss (about five to seven times higher) compared to their normal gravity counterparts because of larger flame size in microgravity and larger convective heat loss fraction from the flame in normal gravity. These studies, however, were confined to laminar flames. For the case of turbulent flames, the flame radiation is a function of time and both the time-averaged and time-dependent components are of interest. In this paper, attention is focused primarily on the time-averaged level of the radiation but the turbulent structure of the flame is also assessed from considerations of the radiation power spectra.

  13. The propagation of premixed flames in closed tubes

    NASA Astrophysics Data System (ADS)

    Matalon, Moshe; Metzener, Philippe

    1997-04-01

    A nonlinear evolution equation that describes the propagation of a premixed flame in a closed tube has been derived from the general conservation equations. What distinguishes it from other similar equations is a memory term whose origin is in the vorticity production at the flame front. The two important parameters in this equation are the tube's aspect ratio and the Markstein parameter. A linear stability analysis indicates that when the Markstein parameter [alpha] is above a critical value [alpha]c the planar flame is the stable equilibrium solution. For [alpha] below [alpha]c the planar flame is no longer stable and there is a band of growing modes. Numerical solutions of the full nonlinear equation confirm this conclusion. Starting with random initial conditions the results indicate that, after a short transient, a at flame develops when [alpha]>[alpha]c and it remains flat until it reaches the end of the tube. When [alpha]<[alpha]c, on the other hand, stable curved flames may develop down the tube. Depending on the initial conditions the flame assumes either a cellular structure, characterized by a finite number of cells convex towards the unburned gas, or a tulip shape characterized by a sharp indentation at the centre of the tube pointing toward the burned gases. In particular, if the initial conditions are chosen so as to simulate the elongated finger-like flame that evolves from an ignition source, a tulip flame evolves downstream. In accord with experimental observations the tulip shape forms only after the flame has travelled a certain distance down the tube, it does not form in short tubes and its formation depends on the mixture composition. While the initial deformation of the flame front is a direct result of the hydrodynamic instability, the actual formation of the tulip flame results from the vortical motion created in the burned gas which is a consequence of the vorticity produced at the flame front.

  14. New insulins and quality of life.

    PubMed

    Iafusco, Dario

    2003-01-01

    Extreme customization of treatment is even more necessary when dealing with young diabetic patients as compared with adult patients. From diagnosis the pediatrician must introduce treatment in the less traumatic way possible so that the child does not perceive a derangement of his/her life. In order to preserve the quality of life the diabetic child must be able to attend birthday parties, participate in sports, and generally lead a full social life just like his/her friends. In the present paper we evaluate the characteristics of the new insulin analogues and their advantages and disadvantages with respect to the needs of patients. The wide spectrum of available insulin formulations including also the new short- and long- acting insulin analogues are of great help in conceiving a therapeutic plan closely adherent to the patient's needs. As an example, in children aged less than 5-6 years a short acting insulin may be injected immediatly after the meal. The same insulin may be useful in older patients with an incostant style of life due to social activities. On the other hand the "old" insulins may still be used for the therapeutic plan in patients with a more constant life style as to the physical exercise and intervals between the meals. In conclusion, the quality of life in the children and adolescents with diabetes may be accomplished with a flexible and personalized therapeutic plan and a great attention to the education. The latter is a very important tool for the compliance and the reduction of anxiety in patients and their parents.

  15. Insulin Human Inhalation

    MedlinePlus

    Insulin inhalation is used in combination with a long-acting insulin to treat type 1 diabetes (condition in which the body does not produce insulin and therefore cannot control the amount of sugar ...

  16. Giving an insulin injection

    MedlinePlus

    ... want. Put the needle into and through the rubber top of the insulin bottle. Push the plunger ... longer-acting insulin. Put the needle into the rubber top of that insulin bottle. Push the plunger ...

  17. Dynamic properties of combustion instability in a lean premixed gas-turbine combustor.

    PubMed

    Gotoda, Hiroshi; Nikimoto, Hiroyuki; Miyano, Takaya; Tachibana, Shigeru

    2011-03-01

    We experimentally investigate the dynamic behavior of the combustion instability in a lean premixed gas-turbine combustor from the viewpoint of nonlinear dynamics. A nonlinear time series analysis in combination with a surrogate data method clearly reveals that as the equivalence ratio increases, the dynamic behavior of the combustion instability undergoes a significant transition from stochastic fluctuation to periodic oscillation through low-dimensional chaotic oscillation. We also show that a nonlinear forecasting method is useful for predicting the short-term dynamic behavior of the combustion instability in a lean premixed gas-turbine combustor, which has not been addressed in the fields of combustion science and physics.

  18. Formation and role of cool flames in plasma-assisted premixed combustion

    NASA Astrophysics Data System (ADS)

    Kim, W.; Mungal, M. G.; Cappelli, M. A.

    2008-02-01

    The structure of a plasma-assisted laminar premixed flame is studied numerically. The initial radical yield generated by a nonequilibrium discharge serves as the boundary condition for a one-dimensional flame code predicting the formation of a cool flame which pilots the premixed methane/air combustion. The ignition of the surrounding unactivated methane-air mixture by this cool flame is modeled as an opposed diffusion flame. Our findings indicate that the nonequilibrium discharge is an in situ reformer of the fuel for the production of the cool flame, producing primarily H2 and CO, thus, facilitating the burning of the lean methane-air mixture.

  19. Pdf modeling for premixed turbulent combustion based on the properties of iso-concentration surfaces

    NASA Technical Reports Server (NTRS)

    Vervisch, L.; Kollmann, W.; Bray, K. N. C.; Mantel, T.

    1994-01-01

    In premixed turbulent flames the presence of intense mixing zones located in front of and behind the flame surface leads to a requirement to study the behavior of iso-concentration surfaces defined for all values of the progress variable (equal to unity in burnt gases and to zero in fresh mixtures). To support this study, some theoretical and mathematical tools devoted to level surfaces are first developed. Then a database of direct numerical simulations of turbulent premixed flames is generated and used to investigate the internal structure of the flame brush, and a new pdf model based on the properties of iso-surfaces is proposed.

  20. Assessment of turbulence-chemistry interaction models in the computation of turbulent non-premixed flames

    NASA Astrophysics Data System (ADS)

    Lewandowski, M. T.; Pozorski, J.

    2016-10-01

    The present work reports on the assessment of different turbulence-chemistry interaction closures for the modelling of turbulent non-premixed combustion. Two-dimensional axisymmetric simulations have been carried out based on three different laboratory flames. The methane fueled, piloted jet flame Sandia D, the simple jet syngas flame and the so-called Delft Jet-in-Hot Coflow flame are studied. All the flames can be characterised as non-premixed but differ by some features which are taken into account through appropriate modelling approach.

  1. DNS of premixed turbulent V-flame: coupling spectral and finite difference methods

    NASA Astrophysics Data System (ADS)

    Hauguel, Raphael; Vervisch, Luc; Domingo, Pascale

    2005-01-01

    To allow for a reliable examination of the interaction between velocity fluctuations, acoustics and combustion, a novel numerical procedure is discussed in which a spectral solution of the Navier-Stokes equations is directly associated to a high-order finite difference fully compressible DNS solver (sixth order PADE). Using this combination of high-order solvers with accurate boundary conditions, simulations have been performed where a turbulent premixed V-shape flame develops in grid turbulence. In the light of the DNS results, a sub-model for premixed turbulent combustion is analyzed. To cite this article: R. Hauguel et al., C. R. Mecanique 333 (2005).

  2. Clinical utility of insulin and insulin analogs.

    PubMed

    Sanlioglu, Ahter D; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect--rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes.

  3. Clinical utility of insulin and insulin analogs

    PubMed Central

    Sanlioglu, Ahter D.; Altunbas, Hasan Ali; Balci, Mustafa Kemal; Griffith, Thomas S.; Sanlioglu, Salih

    2013-01-01

    Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes. PMID:23584214

  4. Intra-bubble-combustion. Premixed limit, stage I: dynamics of rapid premixed flame propagation inside a bubble

    NASA Astrophysics Data System (ADS)

    Arias-Zugasti, Manuel

    2003-06-01

    The propagation of a spherically symmetric premixed thin flame inside an initially centrally ignited bubble in an unconfined viscous, incompressible liquid is theoretically analysed. This model focuses on the dynamical competition between the pressure increase produced by the chemical reaction and the pressure decrease induced by the bubble expansion (a consequence of radial momentum conservation). When a balance between these two processes is achieved an oscillatory response may be observed. The conditions leading to such a response are investigated. The effective inertia (the squared ratio between the characteristic liquid response time and the combustion time) is the main parameter governing this evolution. Two qualitatively different behaviours are encountered for large and small effective inertia-parameter. An approximate analytical solution is provided for each limiting case, as well as a correlation for the gaseous state at the end of the process, based on the former approximate solutions. While the system considered is deliberately highly idealized, some of these quantitative and qualitative results are expected to be helpful in the design of intra-bubble-combustion experiments (Rosner D E, Arias-Zugasti M and La Mantia B 2001 Combustion of individual bubbles and submerged gas jets 6th International Microgravity Combustion Workshop (Cleveland, OH, USA, 22-24 May); Rosner D E, Arias-Zugasti M and La Mantia B 2002 Combustion of individual bubbles and submerged gas jets (poster) 29th Symp. (International) on Combustion (Sapporo, Japan, 21-26 July); Rosner D E 1997 Combustion synthesis and material processing Chem. Eng. Edu (ASEE) 31 228) and, ultimately, bubble reactors.

  5. Alternative routes of administration as an approach to improve insulin therapy: update on dermal, oral, nasal and pulmonary insulin delivery.

    PubMed

    Heinemann, L; Pfützner, A; Heise, T

    2001-09-01

    For the past 75 years subcutaneous injections have been the only route of delivery of insulin therapy to diabetic patients. During this time, numerous attempts have been made to explore alternative routes for systemic insulin administration. However, thus far, no feasible other way of non-invasive insulin delivery has been developed. Dermal insulin application does not result in a reproducible and sufficient transfer of insulin across the highly efficient skin barrier. The dream of an "insulin tablet" has also not become a reality, the main problem being digestion and a lack of a specific peptide carrier system in the gut. Nasal insulin application was considered for a number of years as a potential method, because of the rapid absorption of insulin across the nasal mucosa. However, relative bioavailability was low and required use of absorption enhancers and more importantly, the metabolic effect lasted too short to be of clinical usefulness. To date the most promising alternative route of insulin administration, is the pulmonary delivery of insulin by inhalation which will likely lead to a practically usable system within the next few years. For maximal rate of absorption insulin must be applied deep into the lung, i.e., into the alveoli. A considerable number of inhalers (in combination with appropriate insulin formulations), which are ask to generate insulin particles with an appropriate size for pulmonary delivery, are currently in the clinical phase of development. The pharmaco dynamic effects of insulin formulations administered via the lung are comparable to, or even faster than, those of s.c. injected regular insulin or rapid-acting insulin analogues. The relative biopotency of inhaled insulin in most cases is approximately 10%, i.e., the dose of insulin administered must be 10-fold higher than with s.c. application. The published results of clinical trials thus far, indicate that metabolic control is comparable to that of s.c. insulin therapy. As of to

  6. Fluidity of insulin action.

    PubMed

    Elmendorf, Jeffrey S

    2004-06-01

    Unlike the intensive research in pursuit of understanding the molecular mechanisms of insulin signaling and resistance to its biological action associated most significantly with obesity and type 2 diabetes, the influence of the plasma membrane on insulin sensitivity has been intermittently studied over the years-mainly because it was thought that mediators of insulin action, such as the insulin receptor and the insulin-responsive glucose transporter GLUT4, localize more or less uniformly in the lipids that form cell membranes. Recent insights into membrane physiology suggest that the plasma membrane impacts the function of membrane proteins mediating insulin action. Furthermore, membrane disturbances may be the basis of insulin resistance. Relevant insulin signal transduction data in terms of plasma membrane and insulin resistance are the focus of this review. The discussion visits the cell membrane hypothesis of insulin resistance that suggests insulin action could be related to changes in cell membrane properties.

  7. Insulin binding sites in various segments of the rabbit nephron

    SciTech Connect

    Nakamura, R.; Emmanouel, D.S.; Katz, A.I.

    1983-07-01

    Insulin binds specifically to basolateral renal cortical membranes and modifies tubular electrolyte transport, but the target sites of this hormone in the nephron have not been identified. Using a microassay that permits measurement of hormone binding in discrete tubule segments we have determined the binding sites of /sup 125/I-insulin along the rabbit nephron. Assays were performed under conditions that minimize insulin degradation, and specific binding was measured as the difference between /sup 125/I-insulin bound in the presence or absence of excess (10(-5) M) unlabeled hormone. Insulin monoiodinated in position A14 was used in all assays. Specific insulin binding (attomol . cm-1 +/- SE) was highest in the distal convoluted tubule (180.5 +/- 15.0) and medullary thick ascending limb of Henle's loop (132.9 +/- 14.6), followed by the proximal convoluted and straight tubule. When expressed per milligram protein, insulin binding capacity was highest along the entire thick ascending limb (medullary and cortical portions) and the distal convoluted tubule, i.e., the ''diluting segment'' (congruent to 10(-13) mol . mg protein-1), and was lower (congruent to 4 X 10(-14) mol . mg protein-1), and remarkably similar, in all other nephron segments. Binding specificity was verified in competition studies with unlabeled insulin, insulin analogues (proinsulin and desoctapeptide insulin), and unrelated hormones (glucagon, 1-34 parathyroid hormone, prolactin, follicle-stimulating hormone). In addition, serum containing antiinsulin receptor antibody from two patients with type B insulin resistance syndrome markedly inhibited insulin binding to isolated tubules. Whether calculated per unit tubule length or protein content, insulin binding is highest in the thick ascending limb and the distal convoluted tubule, the same nephron sites where a regulatory role in sodium transport has been postulated for this hormone.

  8. The Biosulin equivalence in standard therapy (BEST) study - a multicentre, open-label, non-randomised, interventional, observational study in subjects using Biosulin 30/70 for the treatment of insulin-dependent type 1 and type 2 diabetes mellitus.

    PubMed

    Segal, D; Tupy, D; Distiller, L

    2013-04-02

    The need for more cost-effective insulin therapy is critical in reducing the burden on patients and health systems. Biosimilar insulins have the potential to dramatically lower healthcare costs by delivering insulin with a similar anti-glycaemic effect and adverse reaction profile. The purpose of this study was to confirm equivalence in glycaemic outcomes and side-effect profiles between Biosulin 30/70 and other human premixed insulin preparations on the South African market in a clinical practice setting. Subjects in this interventional, observational, multicentre, open-label, prospective study were switched from their existing human premix insulin (Actraphane, Humulin 30/70 or Insuman) to the study insulin Biosulin 30/70. The primary endpoint was the change in HbA1c from baseline to 6 months. Seventy-seven adult patients with type 1(n=18) or type 2 (n=59) diabetes were enrolled. The baseline HbA1c in the overall cohort was 7.9%, 8.0% at 3 months (p=0.50) and 7.6% at 6 months (p=0.14).There was a small increase in the total daily dose of insulin used in both the type 1 and type 2 cohort, from 0.62 to 0.65 units/kg/day (p=0.0004). There was no significant difference in weight in the study subjects during the 6-month period on Biosulin 30/70 (p=0.67). Biosulin 30/70 achieved at least equivalent glycaemic control to existing human premix insulins, with no reported new or severe adverse events. Increased use of biosimilar insulins has the potential for significant cost savings.

  9. PTH analogues and osteoporotic fractures.

    PubMed

    Verhaar, Harald J J; Lems, Willem F

    2010-09-01

    At present there are two parathyroid hormone (PTH) analogues (PTH 1 - 34 and PTH 1 - 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 - 34 and PTH 1 - 84) and in men (PTH 1 - 34 only) who are at increased risk of having a fracture. The efficacy and safety of PTH 1 - 34 and PTH 1 - 84 in the management of osteoporosis is evaluated by reviewing published literature and presentations from scientific meetings through to 2010. This review focuses on data on fracture risk reduction and safety endpoints of PTH analogues. The adverse reactions reported most are nausea, pain in the extremities, headache and dizziness. Exogenous PTH analogues, given as daily subcutaneous injections, stimulate bone formation, increase bone mass and bone strength, and improve calcium balance. In postmenopausal women with osteoporosis, PTH analogues reduced the risk of vertebral (PTH 1 - 34 and PTH 1 - 84) and non-vertebral fractures (only PTH 1 - 34). In men and women with glucocorticosteroid-induced osteoporosis, PTH 1 - 34 reduced the risk of vertebral fractures. In general, PTH analogues are well tolerated with an acceptable safety profile: they can be used for the prevention and treatment of fractures in postmenopausal women with severe, established osteoporosis.

  10. High frequency acoustic wave scattering from turbulent premixed flames

    NASA Astrophysics Data System (ADS)

    Narra, Venkateswarlu

    This thesis describes an experimental investigation of high frequency acoustic wave scattering from turbulent premixed flames. The objective of this work was to characterize the scattered incoherent acoustic field and determine its parametric dependence on frequency, flame brush thickness, incident and measurement angles, mean velocity and flame speed. The experimental facility consists of a slot burner with a flat flame sheet that is approximately 15 cm wide and 12 cm tall. The baseline cold flow characteristics and flame sheet statistics were extensively characterized. Studies were performed over a wide range of frequencies (1-24 kHz) in order to characterize the role of the incident acoustic wave length. The spectrum of the scattered acoustic field showed distinct incoherent spectral sidebands on either side of the driving frequency. The scattered incoherent field was characterized in terms of the incoherent field strength and spectral bandwidth and related to the theoretical predictions. The role of the flame front wrinkling scale, i.e., flame brush thickness, was also studied. Flame brush thickness was varied independent of the mean velocity and flame speed by using a variable turbulence generator. Results are reported for five flame brush thickness cases, ranging from 1.2 mm to 5.2 mm. Some dependence of scattered field characteristics on flame brush thickness was observed, but the magnitude of the effect was much smaller than expected from theoretical considerations. The spatial dependence of the scattered field was investigated by measuring the scattered field at four measurement angles and exciting the flame at four incident angles. Theory predicts that these variations influence the spatial scale of the acoustic wave normal to the flame, a result confirmed by the measurements. Measurements were performed for multiple combinations of mean velocities and flame speeds. The scattered field was observed to depend strongly on the flame speed. Further analysis

  11. Non-premixed acoustically perturbed swirling flame dynamics

    SciTech Connect

    Idahosa, Uyi; Saha, Abhishek; Xu, Chengying; Basu, Saptarshi

    2010-09-15

    An investigation into the response of non-premixed swirling flames to acoustic perturbations at various frequencies (f{sub p}=0-315 Hz) and swirl intensities (S=0.09 and 0.34) is carried out. Perturbations are generated using a loudspeaker at the base of an atmospheric co-flow burner with resulting velocity oscillation amplitudes vertical stroke u'/U{sub avg} vertical stroke in the 0.03-0.30 range. The dependence of flame dynamics on the relative richness of the flame is investigated by studying various constant fuel flow rate flame configurations. Flame heat release rate is quantitatively measured using a photomultiplier with a 430 nm bandpass filter for observing CH* chemiluminescence which is simultaneously imaged with a phase-locked CCD camera. The flame response is observed to exhibit a low-pass filter characteristic with minimal flame response beyond pulsing frequencies of 200 Hz. Flames at lower fuel flow rates are observed to remain attached to the central fuel pipe at all acoustic pulsing frequencies. PIV imaging of the associated isothermal fields show the amplification in flame aspect ratio is caused by the narrowing of the inner recirculation zone (IRZ). Good correlation is observed between the estimated flame surface area and the heat release rate signature at higher swirl intensity flame configurations. A flame response index analogous to the Rayleigh criterion in non-forced flames is used to assess the potential for a strong flame response at specific perturbation configurations and is found to be a good predictor of highly responsive modes. Phase conditioned analysis of the flame dynamics yield additional criteria in highly responsive modes to include the effective amplitude of velocity oscillations induced by the acoustic pulsing. In addition, highly responsive modes were characterized by velocity to heat release rate phase differences in the {+-}{pi}/2 range. A final observed characteristic in highly responsive flames is a Strouhal number between

  12. Time-dependent Computational Studies of Premixed Flames in Microgravity

    NASA Technical Reports Server (NTRS)

    Kailasanath, K.; Patnaik, Gopal; Oran, Elaine S.

    1993-01-01

    This report describes the research performed at the Center for Reactive Flow and Dynamical Systems in the Laboratory for Computational Physics and Fluid Dynamics, at the Naval Research Laboratory, in support of NASA Microgravity Science and Applications Program. The primary focus of this research is on investigating fundamental questions concerning the propagation and extinction of premixed flames in earth gravity and in microgravity environments. Our approach is to use detailed time-dependent, multispecies, numerical models as tools to simulate flames in different gravity environments. The models include a detailed chemical kinetics mechanism consisting of elementary reactions among the eight reactive species involved in hydrogen combustion, coupled to algorithms for convection, thermal conduction, viscosity, molecular and thermal diffusion, and external forces. The external force, gravity, can be put in any direction relative to flame propagation and can have a range of values. Recently more advanced wall boundary conditions such as isothermal and no-slip have been added to the model. This enables the simulation of flames propagating in more practical systems than before. We have used the numerical simulations to investigate the effects of heat losses and buoyancy forces on the structure and stability of flames, to help resolve fundamental questions on the existence of flammability limits when there are no external losses or buoyancy forces in the system, to understand the interaction between the various processes leading to flame instabilities and extinguishment, and to study the dynamics of cell formation and splitting. Our studies have been able to bring out the differences between upward- and downward-propagating flames and predict the zero-gravity behavior of these flames. The simulations have also highlighted the dominant role of wall heat losses in the case of downward-propagating flames. The simulations have been able to qualitatively predict the

  13. 21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... SERVICES (CONTINUED) FOOD ADDITIVES Specific Administrative Rulings and Decisions § 170.60 Nitrites and/or nitrates in curing premixes. (a) Nitrites and/or nitrates are food additives when combined in curing... spices, soy products, and spice extractives. Such food additives may be used only after the establishment...

  14. 21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... premixes, may continue to be used under prior sanctions in the commercial curing of meat and meat products... that apply to meat curing preparations for the home curing of meat and meat products, including poultry... hydrolyzed vegetable protein), oleoresins of spices, soy products, and spice extractives. Such food additives...

  15. Premixed Digestion Salts for Kjeldahl Determination of Total Nitrogen in Selected Forest Soils

    Treesearch

    B. G. Blackmon

    1971-01-01

    Estimates of total soil nitrogen by a standard Kjeldahl procedure and a modified procedure employing packets of premixed digestion salts were closely correlated. (r2 = 0.983). The modified procedure appears to be as reliable all the standard method for determining total nitrogen in southern alluvial forest soils.

  16. AROMATIC AND POLYCYCLIC AROMATIC HYDROCARBON FORMATION IN A LAMINAR PREMIXED N-BUTANE FLAME. (R825412)

    EPA Science Inventory

    Abstract

    Experimental and detailed chemical kinetic modeling work has been performed to investigate aromatic and polycyclic aromatic hydrocarbon (PAH) formation pathways in a premixed, rich, sooting, n-butane¯oxygen¯argon burner s...

  17. Analysis of Turbulent Scales of Motion in Premixed Flames Using Structure Functions

    NASA Astrophysics Data System (ADS)

    Hamlington, Peter; Whitman, Samuel; Towery, Colin; Poludnenko, Alexei

    2016-11-01

    Recently, multiscale turbulence-flame interactions in premixed reacting flows have been examined using both physical space and spectral approaches. However, there remains relatively little understanding of how turbulent scales of motion vary through the internal structure of the flame itself (i.e., through premixed flamelets). Such an analysis is made difficult by the inhomogeneity, small scale, and spatial locality of many premixed flames, particularly at high Damköhler and low Karlovitz numbers. Conditional structure functions provide a possible solution to this analysis challenge, and in this talk we present results from the calculation of structure functions using data from highly-resolved direct numerical simulations (DNS) of turbulent premixed flames. The high resolution of the DNS allows structure functions to be calculated normally and tangentially to the local flame surface, revealing the specific effects of the flame on turbulent scales of motion near the scale of the local flame width. Moreover, the conditional nature of the analysis allows the effects of different flame regions (e.g., the preheat and reaction zones) on turbulence to be isolated. The implications of these results for the theory and modeling of turbulent flame physics are outlined.

  18. Influence of particle size on hardening and handling of a premixed calcium phosphate cement.

    PubMed

    Aberg, Jonas; Engstrand, Johanna; Engqvist, Håkan

    2013-04-01

    Premixed calcium phosphate cements (pCPC) have been developed to circumvent problems related to mixing and transfer of cements in the operating room. In addition, by using pCPC the short working times generally associated with conventional water-mixed cements are avoided. In this work, the influence of particle size on handling and hardening characteristics of a premixed monetite cement has been assessed. The cements were evaluated with respect to their injectability, setting time and compressive strength. It was found that cements with smaller particle sizes were more difficult to inject and had higher compressive strength. Regarding setting time, no clear trend could be discerned. The addition of granules made the cements easier to inject, but setting time was prolonged and lower strengths were obtained. The main findings of this work demonstrate that particle size can be used to control handling and physical properties of premixed cements and that previous knowledge from water-based CPC, regarding effects of particle size, is not directly applicable to premixed CPC.

  19. A simulation of a bluff-body stabilized turbulent premixed flame using LES-PDF

    NASA Astrophysics Data System (ADS)

    Kim, Jeonglae; Pope, Stephen

    2013-11-01

    A turbulent premixed flame stabilized by a triangular cylinder as a flame-holder is simulated. The computational condition matches the Volvo experiments (Sjunnesson et al. 1992). Propane is premixed at a fuel lean condition of ϕ = 0 . 65 . For this reactive simulation, LES-PDF formulation is used, similar to Yang et al. (2012). The evolution of Lagrangian particles is simulated by solving stochastic differential equations modeling transport of the composition PDF. Mixing is modeled by the modified IEM model (Viswanathan et al. 2011). Chemical reactions are calculated by ISAT and for the good load balancing, PURAN distribution of ISAT tables is applied (Hiremath et al. 2012). To calculate resolved density, the two-way coupling (Popov & Pope 2013) is applied, solving a transport equation of resolved specific volume to reduce statistical noise. A baseline calculation shows a good agreement with the experimental measurements in turbulence statistics, temperature, and minor species mass fractions. Chemical reaction does not significantly contribute to the overall computational cost, in contrast to non-premixed flame simulations (Hiremath et al. 2013), presumably due to the restricted manifold of the purely premixed flame in the composition space.

  20. AROMATIC AND POLYCYCLIC AROMATIC HYDROCARBON FORMATION IN A LAMINAR PREMIXED N-BUTANE FLAME. (R825412)

    EPA Science Inventory

    Abstract

    Experimental and detailed chemical kinetic modeling work has been performed to investigate aromatic and polycyclic aromatic hydrocarbon (PAH) formation pathways in a premixed, rich, sooting, n-butane¯oxygen¯argon burner s...

  1. Subfilter Scale Combustion Modelling for Large Eddy Simulation of Turbulent Premixed Flames

    NASA Astrophysics Data System (ADS)

    Shahbazian, Nasim

    Large eddy simulation (LES) is a powerful computational tool for modelling turbulent combustion processes. However, for reactive flows, LES is still under significant development. In particular, for turbulent premixed flames, a considerable complication of LES is that the flame thickness is generally much smaller than the LES filter width such that the flame front and chemical reactions cannot be resolved on the grid. Accurate and robust subfilter-scale (SFS) models of the unresolved turbulence-chemistry interactions are therefore required and studies are needed to evaluate and improve them. In this thesis, a detailed comparison and evaluation of five different SFS models for turbulence- chemistry interactions in LES of premixed flames is presented. These approaches include both flamelet- and non-flamelet-based models, coupled with simple or tabulated chemistry. The mod- elling approaches considered herein are: algebraic- and transport-equation variants of the flame surface density (FSD) model, the presumed conditional moment (PCM) with flame prolongation of intrinsic low-dimensional manifold (FPI) tabulated chemistry, or PCM-FPI approach, evaluated with two different presumed probability density function (PDF) models; and conditional source-term estimation (CSE) approach. The predicted LES solutions are compared to the existing laboratory-scale experimental observation of Bunsen-type turbulent premixed methane-air flames, corresponding to lean and stoichiometric conditions lying from the upper limit of the flamelet regime to well within the thin reaction zones regime of the standard regimes diagram. Direct comparison of different SFS approaches allows investigation of stability and performance of the models, while the weaknesses and strengths of each approach are identified. Evaluation of algebraic and transported FSD models highlights the importance of non-equilibrium transport in turbulent premixed flames. The effect of the PDF type for the reaction progress

  2. Subfilter scale combustion modelling for large eddy simulation of turbulent premixed flames

    NASA Astrophysics Data System (ADS)

    Shahbazian, Nasim

    Large eddy simulation (LES) is a powerful computational tool for modelling turbulent combustion processes. However, for reactive flows, LES is still under significant development. In particular, for turbulent premixed flames, a considerable complication of LES is that the flame thickness is generally much smaller than the LES filter width such that the flame front and chemical reactions cannot be resolved on the grid. Accurate and robust subfilter-scale (SFS) models of the unresolved turbulence-chemistry interactions are therefore required and studies are needed to evaluate and improve them. In this thesis, a detailed comparison and evaluation of five different SFS models for turbulence-chemistry interactions in LES of premixed flames is presented. These approaches include both flamelet- and non-flamelet-based models, coupled with simple or tabulated chemistry. The modelling approaches considered herein are: algebraic- and transport-equation variants of the flame surface density (FSD) model, the presumed conditional moment (PCM) with flame prolongation of intrinsic low-dimensional manifold (FPI) tabulated chemistry, or PCM-FPI approach, evaluated with two different presumed probability density function (PDF) models; and conditional source-term estimation (CSE) approach. The predicted LES solutions are compared to the existing laboratory-scale experimental observation of Bunsen-type turbulent premixed methane-air flames, corresponding to lean and stoichiometric conditions lying from the upper limit of the flamelet regime to well within the thin reaction zones regime of the standard regimes diagram. Direct comparison of different SFS approaches allows investigation of stability and performance of the models, while the weaknesses and strengths of each approach are identified. Evaluation of algebraic and transported FSD models highlights the importance of non-equilibrium transport in turbulent premixed flames. The effect of the PDF type for the reaction progress

  3. The application of near-infrared spectroscopy for the quality control analysis of rocket propellant fuel pre-mixes.

    PubMed

    Judge, Michael D

    2004-03-10

    The viability of near-infrared (NIR) spectroscopy as a technique for the quality control analysis of ingredient concentrations in a rocket propellant fuel liquid pre-mix was investigated. The pre-mix analyzed consisted of a polybutadiene pre-polymer, a plasticizer and two antioxidants. It was determined that NIR spectroscopy offered a fast and convenient method of verifying the percentage level of all four ingredients while requiring no sample preparation. The NIR methodology exhibited a high level of accuracy and precision. There was also a clear indication that the technique allowed monitoring of antioxidant depletion in the pre-mix on ageing.

  4. Agonism and Antagonism at the Insulin Receptor

    PubMed Central

    Knudsen, Louise; Hansen, Bo Falck; Jensen, Pia; Pedersen, Thomas Åskov; Vestergaard, Kirsten; Schäffer, Lauge; Blagoev, Blagoy; Oleksiewicz, Martin B.; Kiselyov, Vladislav V.; De Meyts, Pierre

    2012-01-01

    Insulin can trigger metabolic as well as mitogenic effects, the latter being pharmaceutically undesirable. An understanding of the structure/function relationships between insulin receptor (IR) binding and mitogenic/metabolic signalling would greatly facilitate the preclinical development of new insulin analogues. The occurrence of ligand agonism and antagonism is well described for G protein-coupled receptors (GPCRs) and other receptors but in general, with the exception of antibodies, not for receptor tyrosine kinases (RTKs). In the case of the IR, no natural ligand or insulin analogue has been shown to exhibit antagonistic properties, with the exception of a crosslinked insulin dimer (B29-B’29). However, synthetic monomeric or dimeric peptides targeting sites 1 or 2 of the IR were shown to be either agonists or antagonists. We found here that the S961 peptide, previously described to be an IR antagonist, exhibited partial agonistic effects in the 1–10 nM range, showing altogether a bell-shaped dose-response curve. Intriguingly, the agonistic effects of S961 were seen only on mitogenic endpoints (3H-thymidine incorporation), and not on metabolic endpoints (14C-glucose incorporation in adipocytes and muscle cells). The agonistic effects of S961 were observed in 3 independent cell lines, with complete concordance between mitogenicity (3H-thymidine incorporation) and phosphorylation of the IR and Akt. Together with the B29-B’29 crosslinked dimer, S961 is a rare example of a mixed agonist/antagonist for the human IR. A plausible mechanistic explanation based on the bivalent crosslinking model of IR activation is proposed. PMID:23300584

  5. Development of Criteria for Flameholding Tendencies within Premixer Passages for High Hydrogen Content Fuels

    SciTech Connect

    Lewis, Elliot Sullivan-; McDonell, Vincent G.

    2014-12-01

    Due to increasingly stringent air quality requirements stationary power gas turbines have moved to lean-premixed operation, which reduces pollutant emissions but can result in flashback. Flashback can cause serious damage to the premixer hardware. Curtailing flashback can be difficult with hydrocarbon fuels and becomes even more challenging when hydrogen is used as the fuel. The two main approaches for coping with flashback are either to design a combustor that is resistant to flashback, or to design a premixer that will not anchor a flame if flashback occurs. Even with a well-designed combustor flashback can occur under certain circumstances, thus it is necessary to determine how to avoid flameholding within the premixer passageways of a gas turbine. To this end, an experiment was designed that would determine the flameholding propensities at elevated pressures and temperatures of three different classes of geometric features commonly found in gas turbine premixers, with both natural gas and hydrogen fuel. Experiments to find the equivalence ratio at blow off were conducted within an optically accessible test apparatus with four flameholders: 0.25 and 0.50 inch diameter cylinders, a reverse facing step with a height of 0.25 inches, and a symmetric airfoil with a thickness of 0.25 inches and a chord length of one inch. Tests were carried out at temperatures between 300 K and 750 K, at pressures up to 9 atmospheres. Typical bulk velocities were between 40 and 100 m/s. The effect of airfoil’s angle of rotation was also investigated. Blow off for hydrogen flames was found to occur at much lower adiabatic flame temperatures than natural gas flames. Additionally it was observed that at high pressures and high turbulence intensities, reactant velocity does not have a noticeable effect on the point of blow off due in large part to corresponding increases in turbulent flame speed. Finally a semi empirical correlation was developed that predicts flame extinction for both

  6. The role of reactant unmixedness, strain rate, and length scale on premixed combustor performance

    SciTech Connect

    Samuelsen, S.; LaRue, J.; Vilayanur, S.; Guillaume, D.

    1995-12-31

    Lean premixed combustion provides a means to reduce pollutant formation and increase combustion efficiency. However, fuel-air mixing is rarely uniform in space and time. This nonuniformity in concentration will lead to relative increases in pollutant formation and decreases in combustion efficiency. The nonuniformity of the concentration at the exit of the premixer has been defined by Lyons (1981) as the ``unmixedness.`` Although turbulence properties such as length scales and strain rate are known to effect unmixedness, the exact relationship is unknown. Evaluating this relationship and the effect of unmixedness in premixed combustion on pollutant formation and combustion efficiency are an important part of the overall goal of US Department of Energy`s Advanced Turbine System (ATS) program and are among the goals of the program described herein. The information obtained from ATS is intended to help to develop and commercialize gas turbines. The contributions to the program which the University of California (Irvine) Combustion Lab (UCICL) will provide are: (1) establish the relationship of inlet unmixedness, length scales, and mean strain rate to performance, (2) determine the optimal levels of inlet unmixedness, length scales, and mean strain rates to maximize combustor performance, and (3) identify efficient premixing methods for achieving the necessary inlet conditions. The program during this reporting period is focused on developing a means to measure and qualify different degrees of temporal and spatial unmixedness. Laser diagnostic methods for planer unmixedness measurements are being developed and preliminary results are presented herein. These results will be used to (1), aid in the design of experimental premixers, and (2), determine the unmixedness which will be correlated with the emissions of the combustor. This measure of unmixedness coupled with length scale, strain rate and intensity information is required to attain the UCI goals.

  7. Pressor effects of tryptamine analogues.

    PubMed Central

    Bosin, T R; Hixson, E J; Maickel, R P

    1976-01-01

    1. Methylation of tryptamine in the 1-position had little effect on the potency of the drug as a pressor agent in the intact anaesthetized rat. 2. In contrast, substitution of a benzo[b]thiophene ring system for the indole ring decreased the pressor activity. 3. Pretreatment of the animals with reserpine reduced the pressor effect of tryptamine and its benzo[b]thiophene analogue while increasing the effect of the 1-methylindole analogue. 4. Pretreatment with phenoxybenzamine reduced the pressor effect of all three compounds. PMID:1252662

  8. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia.

    PubMed

    Herzberg-Schäfer, S; Heni, M; Stefan, N; Häring, H-U; Fritsche, A

    2012-10-01

    One major risk factor of type 2 diabetes is the impairment of glucose-induced insulin secretion which is mediated by the individual genetic background and environmental factors. In addition to impairment of glucose-induced insulin secretion, impaired glucagon-like peptide (GLP)1-induced insulin secretion has been identified to be present in subjects with diabetes and impaired glucose tolerance, but little is known about its fundamental mechanisms. The state of GLP1 resistance is probably an important mechanism explaining the reduced incretin effect observed in type 2 diabetes. In this review, we address methods that can be used for the measurement of insulin secretion in response to GLP1 in humans, and studies showing that specific diabetes risk genes are associated with resistance of the secretory function of the β-cell in response to GLP1 administration. Furthermore, we discuss other factors that are associated with impaired GLP1-induced insulin secretion, for example, insulin resistance. Finally, we provide evidence that hyperglycaemia per se, the genetic background and their interaction result in the development of GLP1 resistance of the β-cell. We speculate that the response or the non-response to therapy with GLP1 analogues and/or dipeptidyl peptidase-4 (DPP-IV) inhibitors is critically dependent on GLP1 resistance.

  9. Histopathological nerve and skeletal muscle changes in rats subjected to persistent insulin-induced hypoglycemia

    PubMed Central

    Jensen, Vivi Flou Hjorth; Mølck, Anne-Marie; Heydenreich, Annette; Jensen, Karin Juul; Bertelsen, Line Olrik; Alifrangis, Lene; Andersen, Lene; Søeborg, Henrik; Chapman, Melissa; Lykkesfeldt, Jens; Bøgh, Ingrid Brück

    2015-01-01

    New insulin analogues with a longer duration of action and a flatter pharmacodynamic profile are developed to improve convenience and safety for diabetic patients. During the nonclinical development of such analogues, safety studies must be conducted in nondiabetic rats, which consequently are rendered chronically hypoglycemic. A rat comparator model using human insulin would be valuable, as it would enable differentiation between effects related to either persistent insulin-induced hypoglycemia (IIH) or a new analogue per se. Such a model could alleviate the need for an in-study-comparator and thereby reduce the number of animals used during development. Thus, the aims of the present study were i) to develop a preclinical animal model of persistent hypoglycemia in rats using human insulin infusion for four weeks and ii) to investigate histopathological changes in sciatic nerves and quadriceps femoris muscle tissue, as little is known about the response to persistent hypoglycemia in these tissues. Histopathologic changes in insulin-infused animals included axonal degeneration and myofibre degeneration. To our knowledge, this is the first study to show that persistent IIH provokes peripheral nerve and skeletal myofiber degeneration within the same animals. This suggests that the model can serve as a nonclinical comparator model during development of long-acting insulin analogues. PMID:26989298

  10. Rational steering of insulin binding specificity by intra-chain chemical crosslinking

    NASA Astrophysics Data System (ADS)

    Viková, Jitka; Collinsová, Michaela; Kletvíková, Emília; Buděšínský, Miloš; Kaplan, Vojtěch; Žáková, Lenka; Veverka, Václav; Hexnerová, Rozálie; Aviñó, Roberto J. Tarazona; Straková, Jana; Selicharová, Irena; Vaněk, Václav; Wright, Daniel W.; Watson, Christopher J.; Turkenburg, Johan P.; Brzozowski, Andrzej M.; Jiráček, Jiří

    2016-01-01

    Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22–B30 segment, using the CuI-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26–B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormone’s B-chain C-terminus for its IR-B specificity.

  11. Rational steering of insulin binding specificity by intra-chain chemical crosslinking

    PubMed Central

    Viková, Jitka; Collinsová, Michaela; Kletvíková, Emília; Buděšínský, Miloš; Kaplan, Vojtěch; Žáková, Lenka; Veverka, Václav; Hexnerová, Rozálie; Aviñó, Roberto J. Tarazona; Straková, Jana; Selicharová, Irena; Vaněk, Václav; Wright, Daniel W.; Watson, Christopher J.; Turkenburg, Johan P.; Brzozowski, Andrzej M.; Jiráček, Jiří

    2016-01-01

    Insulin is a key hormone of human metabolism with major therapeutic importance for both types of diabetes. New insulin analogues with more physiological profiles and better glycemic control are needed, especially analogues that preferentially bind to the metabolic B-isoform of insulin receptor (IR-B). Here, we aimed to stabilize and modulate the receptor-compatible conformation of insulin by covalent intra-chain crosslinking within its B22–B30 segment, using the CuI-catalyzed Huisgen 1,3-dipolar cycloaddition reaction of azides and alkynes. This approach resulted in 14 new, systematically crosslinked insulin analogues whose structures and functions were extensively characterized and correlated. One of the analogues, containing a B26–B29 triazole bridge, was highly active in binding to both IR isoforms, with a significant preference for IR-B. Our results demonstrate the potential of chemistry-driven modulation of insulin function, also shedding new light on the functional importance of hormone’s B-chain C-terminus for its IR-B specificity. PMID:26792393

  12. Insulin Glargine 300 U/mL: A Review in Diabetes Mellitus.

    PubMed

    Blair, Hannah A; Keating, Gillian M

    2016-03-01

    Insulin glargine 300 U/mL (Toujeo(®)) is a long-acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamic profile than insulin glargine 100 U/mL (Lantus(®)), with a duration of glucose-lowering activity exceeding 24 h. In several 6-month phase III trials, insulin glargine 300 U/mL achieved comparable glycaemic control to that seen with insulin glargine 100 U/mL in patients with type 1 or type 2 diabetes, albeit with consistently higher daily basal insulin requirements. These improvements in glycaemic control were maintained during longer-term (12 months) treatment. Insulin glargine 300 U/mL was generally associated with a lower risk of nocturnal hypoglycaemia than insulin glargine 100 U/mL in insulin-experienced patients with type 2 diabetes, while the risk of nocturnal hypoglycaemia did not significantly differ between treatment groups in insulin-naïve patients with type 2 diabetes or in patients with type 1 diabetes. To conclude, once-daily subcutaneous insulin glargine 300 U/mL is an effective and generally well tolerated basal insulin therapy option for patients with type 1 or type 2 diabetes.

  13. Poly(epsilon-caprolactone)/eudragit nanoparticles for oral delivery of aspart-insulin in the treatment of diabetes.

    PubMed

    Damgé, Christiane; Socha, Marie; Ubrich, Nathalie; Maincent, Philippe

    2010-02-01

    Nanoparticles prepared with a blend of a biodegradable polyester (poly(epsilon-caprolactone)) and a polycationic nonbiodegradable acrylic polymer (Eudragit RS) have been used as a drug carrier for oral administration of a short-acting insulin analogue, aspart-insulin. Insulin-loaded nanoparticles, about 700 nm in diameter, encapsulated 97.5% of insulin and were able to release about 70% of their content in vitro in a neutral medium over 24 h. When administered orally to diabetic rats, insulin-loaded nanoparticles (50 IU/kg) decreased fasted glycemia for a prolonged period of time and improved the glycemic response to glucose in a time-dependent manner, with a maximal effect between 12 and 24 h after their administration. In parallel, plasma insulin levels increased. However, higher (100 IU/kg) and lower (25 IU/kg) doses of insulin did not exert any biological effect. It is concluded that polymeric nanoparticles composed of poly(epsilon-caprolactone)/Eudragit RS are able to preserve the biological activity of the insulin analogue aspart-insulin; however, the postprandial peak suppression was prolonged more than 24 h by comparison with regular insulin working only 6-8 h. This effect may be explained by the monomeric configuration of aspart-insulin, which is probably better taken up by the intestinal mucosa than regular insulin. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

  14. Cost-effectiveness of insulin degludec compared with insulin glargine for patients with type 2 diabetes treated with basal insulin - from the UK health care cost perspective.

    PubMed

    Evans, M; Wolden, M; Gundgaard, J; Chubb, B; Christensen, T

    2014-04-01

    The aim of this analysis was to evaluate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine (IGlar) in adults with type 2 diabetes mellitus (T2DM) who are considered appropriate for treatment with a basal insulin analogue, using a short-term economic model. Meta-analysis data from three phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg versus IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. IDeg is a cost-effective treatment option versus IGlar in patients with T2DM using basal insulin. Base case incremental cost-effectiveness ratios (ICERs) were estimated at £15,795 per quality-adjusted life-year (QALY) and £13,078 per QALY, which are below commonly accepted thresholds for cost-effectiveness. Sensitivity analyses demonstrated that hypoglycaemia event rates had an important effect on the results. With higher event rates for non-severe hypoglycaemia IDeg was less costly and more effective than IGlar (dominant). Conversely, using lower event rates for severe hypoglycaemia generated higher ICERs. Using hypoglycaemia rates from a subgroup of patients who experienced ≥1 hypoglycaemic event per year IDeg was highly cost-effective versus IGlar; with estimated ICERS of £4887 and £2625 per QALY. This short-term modelling approach allows the economic evaluation of newer insulin analogues when advanced long-term modelling based on HbA1c differences is inappropriate. For patients with T2DM who are considered appropriate for treatment with a basal insulin analogue, IDeg is a cost-effective treatment option compared with IGlar and offers additional benefits to subgroups of patients, such as those suffering from recurrent hypoglycaemia. © 2014 John Wiley & Sons Ltd.

  15. Fucosterol activates the insulin signaling pathway in insulin resistant HepG2 cells via inhibiting PTP1B.

    PubMed

    Jung, Hyun Ah; Bhakta, Himanshu Kumar; Min, Byung-Sun; Choi, Jae Sue

    2016-10-01

    Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. This study investigated the modulatory effects of fucosterol on the insulin signaling pathway in insulin-resistant HepG2 cells by inhibiting protein tyrosine phosphatase 1B (PTP1B). In addition, molecular docking simulation studies were performed to predict binding energies, the specific binding site of fucosterol to PTP1B, and to identify interacting residues using Autodock 4.2 software. Glucose uptake was determined using a fluorescent D-glucose analogue and the glucose tracer 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose, and the signaling pathway was detected by Western blot analysis. We found that fucosterol enhanced insulin-provoked glucose uptake and conjointly decreased PTP1B expression level in insulin-resistant HepG2 cells. Moreover, fucosterol significantly reduced insulin-stimulated serine (Ser307) phosphorylation of insulin receptor substrate 1 (IRS1) and increased phosphorylation of Akt, phosphatidylinositol-3-kinase, and extracellular signal- regulated kinase 1 at concentrations of 12.5, 25, and 50 µM in insulin-resistant HepG2 cells. Fucosterol inhibited caspase-3 activation and nuclear factor kappa B in insulin-resistant hepatocytes. These results suggest that fucosterol stimulates glucose uptake and improves insulin resistance by downregulating expression of PTP1B and activating the insulin signaling pathway. Thus, fucosterol has potential for development as an anti-diabetic agent.

  16. Lean Premixed Combustion Stabilized by Low Swirl a Promising Concept for Practical Applications

    NASA Technical Reports Server (NTRS)

    Cheng, R. K.

    1999-01-01

    Since its inception, the low-swirl burner (LSB) has shown to be a useful laboratory apparatus for fundamental studies of premixed turbulent flames. The LSB operates under wide ranges of equivalence ratios, flow rates, and turbulence intensities. Its flame is lifted and detached from the burner and allows easy access for laser diagnostics. The flame brush is axisymmetric and propagates normal to the incident reactants. Therefore, the LSB is well suited for investigating detailed flame structures and empirical coefficients such as flame speed, turbulence transport, and flame generated turbulence. Due to its capability to stabilize ultra-lean premixed turbulent flames (phi approx. = 0.55), the LSB has generated interest from the gas appliance industry for use as an economical low-NO(x) burner. Lean premixed combustion emits low levels of NO(x), due primarily to the low flame temperature. Therefore, it is a very effective NO(x) prevention method without involving selective catalytic reduction (SCR), fuel-air staging, or flue gas recirculation (FGR). En the gas turbine industry, substantial research efforts have already been undertaken and engines with lean premixed combustors are already in use. For commercial and residential applications, premixed pulsed combustors and premixed ceramic matrix burners are commercially available. These lean premixed combustion technologies, however, tend to be elaborate but have relatively limited operational flexibility, and higher capital, operating and maintenance costs. Consequently, these industries are continuing the development of lean premixed combustion technologies as well as exploring new concepts. This paper summarizes the research effects we have undertaken in the past few years to demonstrate the feasibility of applying the low-swirl flame stabilization method for a wide range of heating and power generation systems. The principle of flame stabilization by low-swirl is counter to the conventional high-swirl methods that

  17. Murder by insulin: suspected, purported and proven-a review.

    PubMed

    Marks, Vincent

    2009-04-01

    Murder by insulin-whether attempted, suspected or proven-is rare. Only 66 cases worldwide could be found for this review. A conviction was secured in 31 cases and additional weapon was employed in 11. Differentiation of attempted homicide from Munchausen syndrome by proxy in the young and from 'mercy killing' in the elderly was not attempted. Most perpetrators were close relatives and most victims were alive when discovered and responded to treatment. Hypoglycaemia is the first clue to homicidal insulin use in living subjects and requires the demonstration of a plasma insulin concentration of generally more than 1000 pmol/L and undetectable plasma C-peptide concentration to establish the diagnosis. Serum glucose measurements are valueless in victims found dead. The presence near the body of insulin vials, syringes or needles, loose talk by the suspected perpetrator or their ready access to insulin may be the only clue. The demonstration of insulin in tissue around an injection site by immunohistopathology or by measuring it in an extract clinches the diagnosis. Immunoassays suitable for clinical use to detect and measure insulin and C-peptide are subject to random errors and cannot be relied upon unless special precautions including separation by gel filtration or HPLC are undertaken prior to analysis. They do not detect or measure accurately a new generation of synthetic insulin analogues. Mass spectrometry will be required to do this and to validate clinical immunoassays, upon which convictions have always had to rely in the past. Copyright 2009 John Wiley & Sons, Ltd.

  18. Insulin use in NIDDM.

    PubMed

    Genuth, S

    1990-12-01

    The effects of insulin treatment on the pathophysiology of non-insulin-dependent diabetes mellitus (NIDDM) are reviewed herein. Short-term studies indicate variable and partial reduction in excessive hepatic glucose output, decrease in insulin resistance, and enhancement of beta-cell function. These beneficial actions may be due to a decrease in secondary glucose toxicity rather than a direct attack on the primary abnormality. Insulin should be used as initial treatment of new-onset NIDDM in the presence of ketosis, significant diabetes-induced weight loss (despite residual obesity), and severe hyperglycemic symptoms. In diet-failure patients, prospective randomized studies comparing insulin to sulfonylurea treatment show approximately equal glycemic outcomes or a slight advantage to insulin. A key goal of insulin therapy is to normalize the fasting plasma glucose level. In contrast to the conventional use of morning injections of intermediate- and long-acting insulin, preliminary studies suggest potential advantages of administering the same insulins only at bedtime. Obese patients may require several hundred units of insulin daily and still not achieve satisfactory control. In some, addition of a sulfonylurea to insulin may reduce hyperglycemia, the insulin dose, or both. However, long-term benefits from such combination therapy remain to be demonstrated conclusively. Established adverse effects of insulin treatment in NIDDM are hypoglycemia, particularly in the elderly, and weight gain. Self-monitoring of blood glucose can identify patients in whom excessive weight gain is caused by subtle hypoglycemia. Whether insulin causes weight gain by direct effects on appetite or energy utilization remains controversial. A potential adverse effect of insulin has been suggested by epidemiological studies showing associations between hyperinsulinemia or insulin resistance and increased risk for coronary artery disease, stroke, and hypertension. Although potential mechanisms

  19. Non-premixed conditions in the flameholding recirculation region behind a step in supersonic flow

    NASA Astrophysics Data System (ADS)

    Thakur, Amit

    Flameholding in supersonic flow depends on local conditions in the recirculation region, and on mass transfer into and out of this region. Large gradients in local gas composition and temperature exist in the recirculation region. Hence, stability parameter correlations developed for premixed flames cannot be used to determine blowout stability limits for non-premixed flames encountered in practical devices. In the present study, mixture samples were extracted at different locations in the recirculation region and the shear layer formed behind a rearward-facing step in supersonic flow, and analyzed by mass spectrometry to determine the species concentration distribution in the region. The point-wise mass spectrometer measurements were complemented by acetone planar laser-induced fluorescence (PLIF) measurements to get a planar distribution of fuel mole fraction in the recirculation region. Non-reacting flow tests and combustion experiments were performed by varying various fuel related parameters such as injection location, injection pressure and fuel type. Fuel injection upstream of the step was not effective in supplying enough fuel to the recirculation region and did not sustain the flame in combustion experiments. Fuel injection at the step base was effective in sustaining the flame. For base injection, the local fuel mole fraction in the recirculation region determined from experiments was an order of magnitude higher than the global fuel mole fraction based on total moles of air flowing through the test section and total fuel injected in the test section. This suggests substantial difference in flame stability curve for non-premixed conditions in the scramjet engine compared to premixed flow. For base injection, fuel remained in the recirculation region even at higher injection pressure. Due to slower diffusion rate, the heavier fuel had higher local mole fraction in the recirculation region compared to lighter fuel for a unit global fuel mole fraction

  20. Human insulin genome sequence map, biochemical structure of insulin for recombinant DNA insulin.

    PubMed

    Chakraborty, Chiranjib; Mungantiwar, Ashish A

    2003-08-01

    Insulin is a essential molecule for type I diabetes that is marketed by very few companies. It is the first molecule, which was made by recombinant technology; but the commercialization process is very difficult. Knowledge about biochemical structure of insulin and human insulin genome sequence map is pivotal to large scale manufacturing of recombinant DNA Insulin. This paper reviews human insulin genome sequence map, the amino acid sequence of porcine insulin, crystal structure of porcine insulin, insulin monomer, aggregation surfaces of insulin, conformational variation in the insulin monomer, insulin X-ray structures for recombinant DNA technology in the synthesis of human insulin in Escherichia coli.

  1. 5-Stabilized phosphatidylinositol 3,4,5-trisphosphate analogues bind Grp1 PH, inhibit phosphoinositide phosphatases, and block neutrophil migration.

    PubMed

    Zhang, Honglu; He, Ju; Kutateladze, Tatiana G; Sakai, Takahiro; Sasaki, Takehiko; Markadieu, Nicolas; Erneux, Christophe; Prestwich, Glenn D

    2010-02-15

    Metabolically stabilized analogues of PtdIns(3,4,5)P3 have shown long-lived agonist activity for cellular events and selective inhibition of lipid phosphatase activity. We describe an efficient asymmetric synthesis of two 5-phosphatase-resistant analogues of PtdIns(3,4,5)P3, the 5-methylene phosphonate (MP) and 5-phosphorothioate (PT). Furthermore, we illustrate the biochemical and biological activities of five stabilized PtdIns(3,4,5)P3 analogues in four contexts. First, the relative binding affinities of the 3-MP, 3-PT, 5-MP, 5-PT, and 3,4,5-PT3 analogues to the Grp1 PH domain are shown, as determined by NMR spectroscopy. Second, the enzymology of the five analogues is explored, showing the relative efficiency of inhibition of SHIP1, SHIP2, and phosphatase and tensin homologue deleted on chromosome 10 (PTEN), as well as the greatly reduced ability of these phosphatases to process these analogues as substrates as compared to PtdIns(3,4,5)P3. Third, exogenously delivered analogues severely impair complement factor C5a-mediated polarization and migration of murine neutrophils. Finally, the new analogues show long-lived agonist activity in mimicking insulin action in sodium transport in A6 cells.

  2. The effect of premixed schedule on the crystal formation of calcium phosphate cement-chitosan composite with added tetracycline.

    PubMed

    Mao, Jing; Liu, Yan; Zhou, Bin; Yao, Liyun

    2008-08-01

    In this study, calcium phosphate cements (CPC) were prepared by mixing cement powders of tetracalcium phosphate (TTCP) with a cement liquid of phosphate acid saline solution. Tetracycline (TTC)-CPC, chitosan-CPC and chitosan-TTC-CPC were investigated with different premixed schedule. It was demonstrate that both TTC and chitosan worked on the phase transition and crystal characteristics. TTCP mixed with phosphate acid saline solution had similar features of Fourier transform-infrared spectrometry (FT-IR) no matter it was mixed with chitosan or TTC or both. TTC premixed with cement liquid or powder had significant different features of FT-IR and 876 cm(-1) seemed to be a special peak for TTC when TTC was premixed with cement liquid. This was also supported by XRD analysis, which showed that TTC premixed with cement liquid improved phase transition of TTCP to OCP. Chitosan, as organic additive, regulates the regular crystal formation and inhibits the phase transition of TTCP to OCP, except when it is mingled with cement liquid premixed with TTC in field scanning electron microscope. It was concluded that the premixed schedule influences the crystal formation and phase transition, which may be associated with its biocompatibility and bioactivities in vivo.

  3. Active postoperative acromegaly: sustained remission after discontinuation of somatostatin analogues

    PubMed Central

    Cardenas-Salas, Jersy

    2016-01-01

    Summary In patients with active acromegaly after pituitary surgery, somatostatin analogues are effective in controlling the disease and can even be curative in some cases. After treatment discontinuation, the likelihood of disease recurrence is high. However, a small subset of patients remains symptom-free after discontinuation, with normalized growth hormone (GH) and insulin-like growth factor (IGF1) levels. The characteristics of patients most likely to achieve sustained remission after treatment discontinuation are not well understood, although limited evidence suggests that sustained remission is more likely in patients with lower GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on an MRI scan and/or in patients who receive long-term treatment. In this report, we describe the case of a 56-year-old female patient treated with lanreotide Autogel for 11 years. Treatment was successfully discontinued, and the patient is currently disease-free on all relevant parameters (clinical, biochemical and tumour status). The successful outcome in this case adds to the small body of literature suggesting that some well-selected patients who receive long-term treatment with somatostatin analogues may achieve sustained remission. Learning points: The probability of disease recurrence is high after discontinuation of treatment with somatostatin analogues. Current data indicate that remission after treatment discontinuation may be more likely in patients with low GH and IGF1 levels before treatment withdrawal, in those who respond well to low-dose treatment, in those without evidence of adenoma on MRI, and/or in patients receiving prolonged treatment. This case report suggests that prolonged treatment with somatostatin analogues can be curative in carefully selected patients. PMID:27933171

  4. Insulin regimens and glycemic control in different parts of Europe over 4years after starting insulin in people with type 2 diabetes: Data from the CREDIT non-interventional study.

    PubMed

    Blonde, Lawrence; Marre, Michel; Vincent, Maya; Brette, Sandrine; Pilorget, Valerie; Danchin, Nicholas; Vespasiani, Giacomo; Home, Philip

    2017-08-31

    A number of insulin regimens are used in type 2 diabetes. This analysis aims to better understand the evolution of insulin therapy in different regions of Europe. Data from people starting any insulin were collected in eastern Europe (EEur: Croatia, Russia, Ukraine), northern Europe (NEur: Finland, Germany, UK) and southern Europe (SEur: France, Italy, Portugal, Spain). Retrospective data on starting insulin and prospective follow-up data were extracted from clinical records. At 4years, 1699 (76.0%) of 2236 eligible people had data. EEur participants were mostly female, younger and had shorter diabetes duration on starting insulin, yet had highest baseline HbA1c and more micro-/macrovascular disease. A majority (60%-64%) in all regions started on basal insulin alone, declining to 30%-38% at 4years, with most switching to basal+mealtime insulin regimen (24%-40%). Higher baseline (28%) and 4-year use (34%) of premix insulin was observed in NEur. Change in HbA1c (SD) ranged from -1.2 (2.1)% (-13 [23]mmol/mol) in NEur to -2.4 (2.0)% (-26 [22]mmol/mol) in EEur. Weight change ranged from +1.9 (8.3) kg in NEur to +3.2 (7.0) kg in SEur. Overall documented hypoglycemia ranged from 0.3 (1.3) to 1.3 (4.4) events/person/6-months (NEur vs. EEur, respectively) and was stable with time. Severe hypoglycemia rates remained low. When starting insulin, HbA1c and prevalence of complications were higher in EEur. Regional differences exist in choice of insulin regimens in Europe. However, people starting insulin improved and sustained their glycemic control regardless of regional differences or insulin regimens used. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Consistent flamelet modeling of differential molecular diffusion for turbulent non-premixed flames

    NASA Astrophysics Data System (ADS)

    Wang, Haifeng

    2016-03-01

    Treating differential molecular diffusion correctly and accurately remains as a great challenge to the modeling of turbulent non-premixed combustion. The aim of this paper is to develop consistent modeling strategies for differential molecular diffusion in flamelet models. Two types of differential molecular diffusion models are introduced, linear differential diffusion models and nonlinear differential diffusion models. A multi-component turbulent mixing layer problem is analyzed in detail to gain insights into differential molecular diffusion and its characteristics, particularly the dependence of differential molecular diffusion on the Reynolds number and the Lewis number. These characteristics are then used to validate the differential molecular diffusion models. Finally, the new models are applied to the modeling of a series of laboratory-scale turbulent non-premixed jet flames with different Reynolds number (Sandia Flames B, C, and D) to further assess the models' performance.

  6. Degree of vaporization using an airblast type fuel injector for a premixed-prevaporized combustor

    NASA Technical Reports Server (NTRS)

    Tacina, R. R.

    1978-01-01

    Vaporization data are presented which could be useful in designing premixed-prevaporized fuel preparation systems for gas turbine combustors. Lean, premixed-prevaporized combustion systems are being developed because they operate with low flame temperatures and, therefore, produce low levels of nitrogen oxides. Parametric tests of the effect of inlet air temperature, length (residence time), reference velocity, pressure and fuel-air ratio on the degree of vaporization are reported. Jet A and Diesel no. 2 fuel were tested. A formula is provided which shows the effect of inlet air temperature, residence time, reference velocity, and pressure on the degree of vaporization for a constant fuel-air ratio of 0.020. The results of the effect of inlet air temperature on the degree of vaporization using Jet A and Diesel no. 2 are nearly identical.

  7. Study of Turbulent Premixed Flame Propagation using a Laminar Flamelet Model

    NASA Technical Reports Server (NTRS)

    Im, H. G.

    1995-01-01

    The laminar flamelet concept in turbulent reacting flows is considered applicable to many practical combustion systems (Linan & Williams 1993). For turbulent premixed combustion, the laminar flamelet regime is valid when turbulent Karlovitz number is less than unity, which is equivalent to stating that the characteristic thickness of the flame is less than that of a Kolmogorov eddy; this is known as the Klimov-Williams criterion (Williams 1985). In such a case, the flame maintains its laminar structure, and the effect of turbulent flow is merely to wrinkle and strain the flame front. The propagating wrinkled premixed flame can then be described as an infinitesimally thin surface dividing the unburnt fresh mixture and the burnt product.

  8. Emissions of oxides of nitrogen from an experimental premixed-hydrogen burner

    NASA Technical Reports Server (NTRS)

    Anderson, D. N.

    1976-01-01

    Flame-tube experiments using premixed hydrogen and air were conducted to determine the emissions of oxides of nitrogen (NOx) resulting from ultralean combustion. Measurements of NOx emissions and combustion efficiency were made for inlet mixture temperatures of 600 and 700 K, pressures of 3.8 x 10 to the 5th power and 5.2 x 10 to the 5th power N/m squared, reference velocities of 15 to 18 m/sec, and equivalence ratios of 0.2 to 0.4. At the 700 K inlet mixture temperature, NOx emissions were 0.06 ppmv, and combustion efficiency was 98 percent at an equivalence ratio of 0.24. The use of a high-blockage (92-percent blockage) flameholder made it possible to conduct tests without upstream burning in the premixing duct for mixtures with equivalence ratios less than 0.4. For richer mixtures upstream burning did occur and prevented further testing.

  9. Recent Advances in Understanding of Thermal Expansion Effects in Premixed Turbulent Flames

    NASA Astrophysics Data System (ADS)

    Sabelnikov, Vladimir A.; Lipatnikov, Andrei N.

    2017-01-01

    When a premixed flame propagates in a turbulent flow, not only does turbulence affect the burning rate (e.g., by wrinkling the flame and increasing its surface area), but also the heat release in the flame perturbs the pressure field, and these pressure perturbations affect the turbulent flow and scalar transport. For instance, the latter effects manifest themselves in the so-called countergradient turbulent scalar flux, which has been documented in various flames and has challenged the combustion community for approximately 35 years. Over the past decade, substantial progress has been made in investigating (a) the influence of thermal expansion in a premixed flame on the turbulent flow and turbulent scalar transport within the flame brush, as well as (b) the feedback influence of countergradient scalar transport on the turbulent burning rate. The present article reviews recent developments in this field and outlines issues to be solved in future research.

  10. Extinction and near-extinction instability of non-premixed tubular flames

    SciTech Connect

    Hu, Shengteng; Pitz, Robert W.; Yu, Wang

    2009-01-15

    Tubular non-premixed flames are formed by an opposed tubular burner, a new tool to study the effects of curvature on extinction and flame instability of non-premixed flames. Extinction of the opposed tubular flames generated by burning diluted H{sub 2}, CH{sub 4} or C{sub 3}H{sub 8} with air is investigated for both concave and convex curvature. To examine the effects of curvature on extinction, the critical fuel dilution ratios at extinction are measured at various stretch rates, initial mixture strengths and flame curvature for fuels diluted in N{sub 2}, He, Ar or CO{sub 2}. In addition, the onset conditions of the cellular instability are mapped as a function of stretch rates, initial mixture strengths, and flame curvature. For fuel mixtures with Lewis numbers much less than unity, such as H{sub 2}/N{sub 2}, concave flame curvature towards the fuel suppresses cellular instabilities. (author)

  11. Effects of operating pressure on flame oscillation and emission characteristics in a partially premixed swirl combustor

    SciTech Connect

    Kim, Jong-Ryul; Choi, Gyung-Min; Kim, Duck-Jool

    2011-01-15

    The influence of varying combustor pressure on flame oscillation and emission characteristics in the partially premixed turbulent flame were investigated. In order to investigate combustion characteristics in the partially premixed turbulent flame, the combustor pressure was controlled in the range of -30 to 30 kPa for each equivalence ratio ({phi} = 0.8-1.2). The r.m.s. of the pressure fluctuations increased with decreasing combustor pressure for the lean condition. The combustor pressure had a sizeable influence on combustion oscillation, whose dominant frequency varied with the combustor pressure. Combustion instabilities could be controlled by increasing the turbulent intensity of the unburned mixture under the lean condition. An unstable flame was caused by incomplete combustion; hence, EICO greatly increased. Furthermore, EINO{sub x} simply reduced with decreasing combustor pressure at a rate of 0.035 g/10 kPa. The possibility of combustion control on the combusting mode and exhaust gas emission was demonstrated. (author)

  12. An investigation of diamond film deposition in a premixed oxyacetylene flame

    NASA Astrophysics Data System (ADS)

    Cappelli, Mark A.; Paul, P. H.

    1989-09-01

    Polycrystalline diamond film synthesis has been demonstrated using a wide variety of enhanced chemical vapor deposition (CVD) techniques. The method of choice depends on the end application of the deposited film or coating. Diamond film has been deposited in a single-nozzle pre-mixed oxy-acetylene flame. Results of runs of varying duration suggest that diamond is deposited via the transport of hydrocarbon fragments produced at the secondary flame front. Planar laser induced photodissociation fluorescence suggests that this region is rich in C2H species. Emission studies also suggest that the post primary flame zone presents a source of C2 radicals which may account for the observed graphite and diamond-like carbon deposited on the substrate exposed to this region of the flame. The results on the pre-mixed flame suggest that it would be possible and more convenient to attempt large area deposition using a multi-nozzle diffusion flame.

  13. Liquid chromatographic determination of amprolium in poultry feed and premixes using postcolumn chemistry with fluorometric detection.

    PubMed

    Vanderslice, J T; Huang, M H

    1987-01-01

    Two extraction and liquid chromatographic procedures are presented which separate amprolium from compounds in poultry feed or premixes that could interfere with its fluorometric determination. The procedures are based on earlier work on the determination of thiamine in food samples. Amprolium is extracted from feed with a hexane-aqueous sulfosalicylic acid mix, separated on a C18 column, and detected fluorometrically after postcolumn derivatization. For premixes, water extraction is used. Values for the amprolium content of poultry feed obtained with these procedures are in good agreement with those obtained with AOAC official methods. It is suggested that these methods with suitable modifications may be of use for routine analysis of amprolium in feeds. The overall methods are rapid and appear to give reasonable results.

  14. Analysis of the flamelet concept in the numerical simulation of laminar partially premixed flames

    SciTech Connect

    Consul, R.; Oliva, A.; Perez-Segarra, C.D.; Carbonell, D.; de Goey, L.P.H.

    2008-04-15

    The aim of this work is to analyze the application of flamelet models based on the mixture fraction variable and its dissipation rate to the numerical simulation of partially premixed flames. Although the main application of these models is the computation of turbulent flames, this work focuses on the performance of flamelet concept in laminar flame simulations removing, in this way, turbulence closure interactions. A well-known coflow methane/air laminar flame is selected. Five levels of premixing are taken into account from an equivalence ratio {phi}={infinity} (nonpremixed) to {phi}=2.464. Results obtained using the flamelet approaches are compared to data obtained from the detailed solution of the complete transport equations using primitive variables. Numerical simulations of a counterflow flame are also presented to support the discussion of the results. Special emphasis is given to the analysis of the scalar dissipation rate modeling. (author)

  15. On the Interaction of a Premixed Flame with an Acoustic Disturbance

    NASA Technical Reports Server (NTRS)

    Hood, Caroline; Frendi, Abdelkader

    2005-01-01

    The main objective of this research is to analyze the effect of acoustic disturbances on a premixed flame and determine their role in the onset of combustion instabilities. Computations for the one-dimensional, unsteady combustion of a lean premixed methane-air mixture are performed. An acoustic excitation is introduced in the chamber and interacts with the flame front. Our results indicate that as the amplitude of the acoustic excitation is increased, the flame front position fluctuates rapidly. This phenomenon is even more intense when the frequency of the acoustic disturbance matches the fundamental frequency of the chamber. Our results suggest that the interactions between the flame and the acoustic excitation may result in flame extinguishment. In addition various passive control devices are tested and we found that the Helmholtz resonator with rounded inlet corners is the most efficient.

  16. Development of lean premixed low-swirl burner for low NO{sub x} practical application

    SciTech Connect

    Yegian, D.T.; Cheng, R.K.

    1999-07-07

    Laboratory experiments have been performed to evaluate the performance of a premixed low-swirl burner (LSB) in configurations that simulate commercial heating appliances. Laser diagnostics were used to investigate changes in flame stabilization mechanism, flowfield, and flame stability when the LSB flame was confined within quartz cylinders of various diameters and end constrictions. The LSB adapted well to enclosures without generating flame oscillations and the stabilization mechanism remained unchanged. The feasibility of using the LSB as a low NO{sub x} commercial burner has also been verified in a laboratory test station that simulates the operation of a water heater. It was determined that the LSB can generate NO{sub x} emissions < 10 ppm (at 3% O{sub 2}) without significant effect on the thermal efficiency of the conventional system. The study has demonstrated that the lean premixed LSB has commercial potential for use as a simple economical and versatile burner for many low emission gas appliances.

  17. Experimental study on the flame behaviors of premixed methane/air mixture in horizontal rectangular ducts

    NASA Astrophysics Data System (ADS)

    Chen, Dongliang; Sun, Jinhua; Chen, Sining; Liu, Yi; Chu, Guanquan

    2007-01-01

    In order to explore the flame propagation characteristics and tulip flame formation mechanism of premixed methane/air mixture in horizontal rectangular ducts, the techniques of Schlieren and high-speed video camera are used to study the flame behaviors of the premixed gases in a closed duct and opened one respectively, and the propagation characteristics in both cases and the formation mechanism of the tulip flame are analyzed. The results show that, the propagation flame in a closed duct is prior to form a tulip flame structure than that in an opened duct, and the tulip flame structure formation in a closed duct is related to the flame propagation velocity decrease. The sharp decrease of the flame propagation velocity is one of the reasons to the tulip flame formation, and the decrease of the flame propagation velocity is due to the decrease of the burned product flow velocity mainly.

  18. PREMIXED FLAME PROPAGATION AND MORPHOLOGY IN A CONSTANT VOLUME COMBUSTION CHAMBER

    SciTech Connect

    Hariharan, A; Wichman, IS

    2014-06-04

    This work presents an experimental and numerical investigation of premixed flame propagation in a constant volume rectangular channel with an aspect ratio of six (6) that serves as a combustion chamber. Ignition is followed by an accelerating cusped finger-shaped flame-front. A deceleration of the flame is followed by the formation of a "tulip"-shaped flame-front. Eventually, the flame is extinguished when it collides with the cold wall on the opposite channel end. Numerical computations are performed to understand the influence of pressure waves, instabilities, and flow field effects causing changes to the flame structure and morphology. The transient 2D numerical simulation results are compared with transient 3D experimental results. Issues discussed are the appearance of oscillatory motions along the flame front and the influences of gravity on flame structure. An explanation is provided for the formation of the "tulip" shape of the premixed flame front.

  19. Relative stability of selenites and selenates in feed premixes as a function of water activity.

    PubMed

    Eisenberg, Sylvan

    2007-01-01

    Sodium selenite is more hygroscopic than sodium selenate. It is, therefore, more likely to dissolve when dispersed in feeds of relatively high water activity. When dissolved, it may form selenious acid and disperse as a vapor. This is easily demonstrated by mounting a filter paper wetted with a reagent such as ascorbic acid over the subject feed, but not in contact with it. The paper turns brown as elemental selenium is formed from reduction of the vapor. Analysis of the paper ensures that the brown is indeed selenium. Though premixes are generally low enough in moisture content to ensure stability of the selenites, this is not true of many feeds. The water activities of a number of feeds, feed premixes, and feed ingredients have been determined instrumentally and compared to those of saturated solutions of sodium selenite and sodium selenate. There is no question that the selenite often dissolves with the potential to react and, in so doing, loses its nutritional function.

  20. Insulin C-peptide

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003701.htm Insulin C-peptide test To use the sharing features ... a product that is created when the hormone insulin is produced and released into the body. The ...

  1. Insulin pump (image)

    MedlinePlus

    The catheter at the end of the insulin pump is inserted through a needle into the abdominal ... with diabetes. Dosage instructions are entered into the pump's small computer and the appropriate amount of insulin ...

  2. Suicide by Insulin?

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_165701.html Suicide by Insulin? Self-harm and suicidal behavior may ... higher rates of depression, the researchers explained. And suicide or suicide attempts using insulin or other diabetes ...

  3. Neuronal Analogues of Conditioning Paradigms

    DTIC Science & Technology

    1984-04-24

    Although the mechanisms of interneuronal communication have been well established, the changes underlying most forms of learning have thus far eluded...stimulating electrodes on one of the connectives was adjusted so as to produce a small excitatory postsynaptic potential ( EPSP ) in the impaled cell...two stimuli would constitute a neuronal analogue of conditioning by producing an increased EPSP in response to the test stimulus alone. If so, then

  4. Desferrithiocin Analogue Uranium Decorporation Agents

    PubMed Central

    Bergeron, Raymond J.; Wiegand, Jan; Singh, Shailendra

    2010-01-01

    Purpose Previous systematic structure-activity studies of the desferrithiocin (DFT) platform have allowed the design and synthesis of analogues and derivatives of DFT that retain the exceptional iron-clearing activity of the parent, while eliminating its adverse effects. We hypothesized that a similar approach could be adopted to identify DFT-related analogues that could effectively decorporate uranium. Materials and Methods The decorporation properties of nine DFT-related analogues were determined in a bile duct-cannulated rat model. Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected ligands also underwent multiple and delayed dosing regimens. Uranium excretion in urine and bile or stool was determined by inductively coupled plasma mass spectroscopy (ICP-MS); tissue levels of uranium were also assessed. Results The two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction on p.o. administration. The majority of the metal excretion promoted by these analogues is in the bile, thus further reducing kidney actinide exposure. Conclusions While 9 administered p.o. or subcutaneously (s.c.) immediately post-metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h reduced the activity of the compound. Conversion of 9 to its isopropyl ester may circumvent this issue. PMID:19399680

  5. Nonlinear hydrodynamic and thermoacoustic oscillations of a bluff-body stabilised turbulent premixed flame

    NASA Astrophysics Data System (ADS)

    Lee, Chin Yik; Li, Larry Kin Bong; Juniper, Matthew P.; Cant, Robert Stewart

    2016-01-01

    Turbulent premixed flames often experience thermoacoustic instabilities when the combustion heat release rate is in phase with acoustic pressure fluctuations. Linear methods often assume a priori that oscillations are periodic and occur at a dominant frequency with a fixed amplitude. Such assumptions are not made when using nonlinear analysis. When an oscillation is fully saturated, nonlinear analysis can serve as a useful avenue to reveal flame behaviour far more elaborate than period-one limit cycles, including quasi-periodicity and chaos in hydrodynamically or thermoacoustically self-excited system. In this paper, the behaviour of a bluff-body stabilised turbulent premixed propane/air flame in a model jet-engine afterburner configuration is investigated using computational fluid dynamics. For the frequencies of interest in this investigation, an unsteady Reynolds-averaged Navier-Stokes approach is found to be appropriate. Combustion is represented using a modified laminar flamelet approach with an algebraic closure for the flame surface density. The results are validated by comparison with existing experimental data and with large eddy simulation, and the observed self-excited oscillations in pressure and heat release are studied using methods derived from dynamical systems theory. A systematic analysis is carried out by increasing the equivalence ratio of the reactant stream supplied to the premixed flame. A strong variation in the global flame structure is observed. The flame exhibits a self-excited hydrodynamic oscillation at low equivalence ratios, becomes steady as the equivalence ratio is increased to intermediate values, and again exhibits a self-excited thermoacoustic oscillation at higher equivalence ratios. Rich nonlinear behaviour is observed and the investigation demonstrates that turbulent premixed flames can exhibit complex dynamical behaviour including quasiperiodicity, limit cycles and period-two limit cycles due to the interactions of various

  6. Kinetic Effects of Non-Equilibrium Plasma on Partially Premixed Flame Extinction

    DTIC Science & Technology

    2011-01-01

    dissociative attachment processes. The Boltzmann equation calculates the rate coefficients of the electron impact elementary reactions by averaging the...ion-ion neutralization processes, ion-molecule reactions, and electron attachment and detachment processes. Note that the present model does not solve...partially premixed methane flames was studied at 60 Torr by blending 2% CH4 into the oxidizer stream. The non-equilibrium discharge accelerated

  7. Low and High Temperature Combustion Chemistry of Butanol Isomers in Premixed Flames and Autoignition Systems

    SciTech Connect

    Sarathy, S M; Pitz, W J; Westbrook, C K; Mehl, M; Yasunaga, K; Curran, H J; Tsujimura, T; Osswald, P; Kohse-Hoinghaus, K

    2010-12-12

    Butanol is a fuel that has been proposed as a bio-derived alternative to conventional petroleum derived fuels. The structural isomer in traditional 'bio-butanol' fuel is n-butanol, but newer conversion technologies produce iso-butanol as a fuel. In order to better understand the combustion chemistry of bio-butanol, this study presents a comprehensive chemical kinetic model for all the four isomers of butanol (e.g., 1-, 2-, iso- and tert-butanol). The proposed model includes detailed high temperature and low temperature reaction pathways. In this study, the primary experimental validation target for the model is premixed flat low-pressure flame species profiles obtained using molecular beam mass spectrometry (MBMS). The model is also validated against previously published data for premixed flame velocity and n-butanol rapid compression machine and shock tube ignition delay. The agreement with these data sets is reasonably good. The dominant reaction pathways at the various pressures and temperatures studied are elucidated. At low temperature conditions, we found that the reaction of alphahydroxybutyl with O{sub 2} was important in controlling the reactivity of the system, and for correctly predicting C{sub 4} aldehyde profiles in low pressure premixed flames. Enol-keto isomerization reactions assisted by HO{sub 2} were also found to be important in converting enols to aldehydes and ketones in the low pressure premixed flames. In the paper, we describe how the structural features of the four different butanol isomers lead to differences in the combustion properties of each isomer.

  8. Premixed Turbulent Combustion in High Reynolds Number Regimes of Thickened Flamelets and Distributed Reactions

    DTIC Science & Technology

    2016-03-24

    regime, while a distributed reaction sub-model may be a better choice to simulate a high-swirl conditions in gas turbine and other types of engines...Reaction zone structures and mixing characteristics of partially premixed swirling CH4/air flames in a gas turbine model combustor, Proceedings of...Prevaporized Gas Turbine Combustor Studied Using Phase-Averaged PIV, Combustion and Flame 161 (2014) 958–970. 49. S. Böckle, J. Kazenwadel, T

  9. Self-organized Spiral and Circular Waves in Premixed Gas Flames

    NASA Technical Reports Server (NTRS)

    Pealman, Howard G.; Ronney, Paul D.

    1994-01-01

    A diffusive-thermal high Lewis number (Le) gas-phase oscillator has been observed in premixed flames using a lean mixture of butane and oxygen diluted with helium (Le approx. 3.0). This reactive-diffusive system exhibits both propagating radial pulsations and rotating spiral waves perhaps,analogous to those observed in other excitable media such as the Belousov-Zhabotinsky reaction.

  10. Self-organized spiral and circular waves in premixed gas flames

    NASA Technical Reports Server (NTRS)

    Pearlman, Howard G.; Ronney, Paul D.

    1994-01-01

    A diffusive-thermal high Lewis number (Le) gas-phase oscillator has been observed in premixed flames using a lean mixture of butane and oxygen diluted with helium (Le approximately equals 3.0). This reactive-diffusive system exhibits both propagating radial pulsations and rotating spiral waves perhaps analogous to those observed in other excitable media such as the Belousov-Zhabotinsky reaction.

  11. Nanosecond Plasma Enhanced H2/O2/N2 Premixed Flat Flames

    DTIC Science & Technology

    2014-01-01

    hole, which defines the spatial resolution of the measurements in the direction normal to laser propagation, and passes into the vacuum chamber...combustion, nanosecond plasma discharge, burner stabilized premixed flame, plasma fluid modeling, Laser Induced Fluorescence, Thermometry. Paper length...is studied at low pressure (25 torr), using a novel plasma-flame facility, non-intrusive laser diagnostics, and high- fidelity numerical simulations

  12. Laser-saturated fluorescence of nitric oxide and chemiluminescence measurements in premixed ethanol flames

    SciTech Connect

    Marques, Carla S.T.; Barreta, Luiz G.; Sbampato, Maria E.; dos Santos, Alberto M.

    2010-11-15

    In this study, nitric oxide laser-saturated fluorescence (LSF) measurements were acquired from premixed ethanol flames at atmospheric pressure in a burner. NO-LSF experimental profiles for fuel-rich premixed ethanol flames ({phi} = 1.34 and {phi} = 1.66) were determined through the excitation/detection scheme of the Q{sub 2}(26.5) rotational line in the A{sup 2}{sigma}{sup +} - X{sup 2}{pi} (0,0) vibronic band and {gamma}(0,1) emission band. A calibration procedure by NO doping into the flame was applied to establish the NO concentration profiles in these flames. Chemiluminescent emission measurements in the (0, 0) vibronic emission bands of the OH{sup *} (A{sup 2}{sigma}{sup +} - X{sup 2}{pi}) and CH{sup *}(A{sup 2}{delta} - X{sup 2}{pi}) radicals were also obtained with high spatial and spectral resolution for fuel-rich premixed ethanol flames to correlate them with NO concentrations. Experimental chemiluminescence profiles and the ratios of the integrated areas under emission spectra (A{sub CH*}/A{sub CH*}(max.) and A{sub CH*}/A{sub OH*}) were determined. The relationships between chemiluminescence and NO concentrations were established along the premixed ethanol flames. There was a strong connection between CH{sup *} radical chemiluminescence and NO formation and the prompt-NO was identified as the governing mechanism for NO production. The results suggest the optimum ratio of the chemiluminescence of two radicals (A{sub CH*}/A{sub OH*}) for NO diagnostic purposes. (author)

  13. On the structure, propagation, and stabilization of laminar premixed flames. Final report

    SciTech Connect

    Law, Chung K.

    1999-07-01

    The primary objective of the funded program was to qualitatively understand and quantitatively determine the structure and dynamics of laminar premixed flames. The investigation was conducted using laser-based experimentation, computational simulation with detailed chemistry and transport, and activation energy asymptotic analysis. Highlights of accomplishments were discussed in the annual reports submitted to the program monitor for this project. Details are reported in the thirty journal publications cited in the journal article list which is the major component of this final report.

  14. Simulations and experiments on the ignition probability in turbulent premixed bluff-body flames

    NASA Astrophysics Data System (ADS)

    Sitte, Michael Philip; Bach, Ellen; Kariuki, James; Bauer, Hans-Jörg; Mastorakos, Epaminondas

    2016-05-01

    The ignition characteristics of a premixed bluff-body burner under lean conditions were investigated experimentally and numerically with a physical model focusing on ignition probability. Visualisation of the flame with a 5 kHz OH* chemiluminescence camera confirmed that successful ignitions were those associated with the movement of the kernel upstream, consistent with previous work on non-premixed systems. Performing many separate ignition trials at the same spark position and flow conditions resulted in a quantification of the ignition probability Pign, which was found to decrease with increasing distance downstream of the bluff body and a decrease in equivalence ratio. Flows corresponding to flames close to the blow-off limit could not be ignited, although such flames were stable if reached from a richer already ignited condition. A detailed comparison with the local Karlovitz number and the mean velocity showed that regions of high Pign are associated with low Ka and negative bulk velocity (i.e. towards the bluff body), although a direct correlation was not possible. A modelling effort that takes convection and localised flame quenching into account by tracking stochastic virtual flame particles, previously validated for non-premixed and spray ignition, was used to estimate the ignition probability. The applicability of this approach to premixed flows was first evaluated by investigating the model's flame propagation mechanism in a uniform turbulence field, which showed that the model reproduces the bending behaviour of the ST-versus-u‧ curve. Then ignition simulations of the bluff-body burner were carried out. The ignition probability map was computed and it was found that the model reproduces all main trends found in the experimental study.

  15. Development and Validation of a Thickened Flame Modeling Approach for Large Eddy Simulation of Premixed Combustion

    SciTech Connect

    Strakey, Peter A.; Eggenspieler, Gilles

    2010-04-07

    The development of a dynamic thickened flame (TF) turbulence-chemistry interaction model is presented based on a novel approach to determine the subfilter flame wrinkling efficiency. The burner is based on an enclosed scaled-down version of the low swirl injector developed at Lawrence Berkeley National Laboratory (LBNL). A perfectly premixed lean methane-air flame was studied, as well as the cold-flow characteristics of the combustor.

  16. Self-organized Spiral and Circular Waves in Premixed Gas Flames

    NASA Technical Reports Server (NTRS)

    Pealman, Howard G.; Ronney, Paul D.

    1994-01-01

    A diffusive-thermal high Lewis number (Le) gas-phase oscillator has been observed in premixed flames using a lean mixture of butane and oxygen diluted with helium (Le approx. 3.0). This reactive-diffusive system exhibits both propagating radial pulsations and rotating spiral waves perhaps,analogous to those observed in other excitable media such as the Belousov-Zhabotinsky reaction.

  17. Self-organized spiral and circular waves in premixed gas flames

    NASA Technical Reports Server (NTRS)

    Pearlman, Howard G.; Ronney, Paul D.

    1994-01-01

    A diffusive-thermal high Lewis number (Le) gas-phase oscillator has been observed in premixed flames using a lean mixture of butane and oxygen diluted with helium (Le approximately equals 3.0). This reactive-diffusive system exhibits both propagating radial pulsations and rotating spiral waves perhaps analogous to those observed in other excitable media such as the Belousov-Zhabotinsky reaction.

  18. Quantification of trace metals in infant formula premixes using laser-induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Cama-Moncunill, Raquel; Casado-Gavalda, Maria P.; Cama-Moncunill, Xavier; Markiewicz-Keszycka, Maria; Dixit, Yash; Cullen, Patrick J.; Sullivan, Carl

    2017-09-01

    Infant formula is a human milk substitute generally based upon fortified cow milk components. In order to mimic the composition of breast milk, trace elements such as copper, iron and zinc are usually added in a single operation using a premix. The correct addition of premixes must be verified to ensure that the target levels in infant formulae are achieved. In this study, a laser-induced breakdown spectroscopy (LIBS) system was assessed as a fast validation tool for trace element premixes. LIBS is a promising emission spectroscopic technique for elemental analysis, which offers real-time analyses, little to no sample preparation and ease of use. LIBS was employed for copper and iron determinations of premix samples ranging approximately from 0 to 120 mg/kg Cu/1640 mg/kg Fe. LIBS spectra are affected by several parameters, hindering subsequent quantitative analyses. This work aimed at testing three matrix-matched calibration approaches (simple-linear regression, multi-linear regression and partial least squares regression (PLS)) as means for precision and accuracy enhancement of LIBS quantitative analysis. All calibration models were first developed using a training set and then validated with an independent test set. PLS yielded the best results. For instance, the PLS model for copper provided a coefficient of determination (R2) of 0.995 and a root mean square error of prediction (RMSEP) of 14 mg/kg. Furthermore, LIBS was employed to penetrate through the samples by repetitively measuring the same spot. Consequently, LIBS spectra can be obtained as a function of sample layers. This information was used to explore whether measuring deeper into the sample could reduce possible surface-contaminant effects and provide better quantifications.

  19. Substrate analogues for isoprenoid enzymes

    SciTech Connect

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  20. Forum for Injection Techniques, India: The First Indian Recommendations for Best Practice in Insulin Injection Technique

    PubMed Central

    Kalra, Sanjay; Balhara, Yatan Pal Singh; Baruah, Manash P.; Chadha, Manoj; Chandalia, Hemraj B.; Chowdhury, Subhankar; Kumar, K. M. Prasanna; Modi, Sonal; Pitale, Shailesh; Shukla, Rishi; Sahay, Rakesh; Sundaram, Annamalai; Unnikrishnan, Ambika G.; Wangnoo, Subhash K.

    2012-01-01

    Advances in the treatment of diabetes have led to an increase in the number of injectable therapies, such as human insulin, insulin analogues, and glucagon-like peptide-1 analogues. The efficacy of injection therapy in diabetes depends on correct injection technique, among many other factors. Good injection technique is vital in achieving glycemic control and thus preventing complications of diabetes. From the patients’ and health-care providers’ perspective, it is essential to have guidelines to understand injections and injection techniques. The abridged version of the First Indian Insulin Injection technique guidelines developed by the Forum for Injection Technique (FIT) India presented here acknowledge good insulin injection techniques and provide evidence-based recommendations to assist diabetes care providers in improving their clinical practice. PMID:23226630

  1. Optimization of instant dalia dessert pre-mix production by using response surface methodology.

    PubMed

    Jha, Alok; Shalini, B N; Patel, Ashok Ambalal; Singh, Mithilesh; Rasane, Prasad

    2015-02-01

    Dalia, a wheat-based, particulate containing dairy dessert is popularly consumed as a breakfast food and is also considered as a health food. Though popular throughout Northern parts of the country, its limited shelf-life even under refrigeration imposes severe restrictions on its organized manufacture and marketing. In order to promote dalia dessert as a marketable product, in the present study, a process was developed for manufacture of instant dalia pre-mix, as a dry product with long shelf-life, which could be attractively packaged and easily reconstituted for consumption. During the investigation, the effect of different levels of milk solids and wheat solids was studied on dalia pre-mix quality by employing a central composite rotatable design (CCRD). The suggested formulation had 17.82 % milk solids and 2.87 % wheat solids. This formulation was found to be most appropriate for manufacture of instant dalia pre-mix with predicted sensory scores (Max. 100) of 85.35, 41.98 and 67.27 for mouthfeel, consistency and flavor, respectively; the viscosity of the product was 941.0 cp.

  2. Prediction of electron and ion concentrations in low-pressure premixed acetylene and ethylene flames

    NASA Astrophysics Data System (ADS)

    Cancian, J.; Bennett, B. A. V.; Colket, M. B.; Smooke, M. D.

    2013-04-01

    Flame stabilisation and extinction in a number of different flows can be affected by application of electric fields. Electrons and ions are present in flames, and because of charge separation, weak electric fields can also be generated even when there is no externally applied electric field. In this work, a numerical model incorporating ambipolar diffusion and plasma kinetics has been developed to predict gas temperature, species, and ion and electron concentrations in laminar premixed flames without applied electric fields. This goal has been achieved by combining the existing CHEMKIN-based PREMIX code with a recently developed methodology for the solution of electron temperature and transport properties that uses a plasma kinetics model and a Boltzmann equation solver. A chemical reaction set has been compiled from seven sources and includes chemiionisation, ion-molecule, and dissociative-recombination reactions. The numerical results from the modified PREMIX code (such as peak number densities of positive ions) display good agreement with previously published experimental data for fuel-rich, non-sooting, low-pressure acetylene and ethylene flames without applied electric fields.

  3. How ''flat'' is the rich premixed flame produced by your McKenna burner?

    SciTech Connect

    Migliorini, F.; De Iuliis, S.; Cignoli, F.; Zizak, G.

    2008-05-15

    McKenna burners are widely used in the combustion community for producing ''flat'' premixed flames. These flames are considered as standards for the development and calibration of optical techniques. Rich premixed flames produced by McKenna burners are frequently investigated in order to understand soot formation processes both by optical and by sampling techniques. Measurements are normally performed along the axis of the flames, with a uniform distribution of temperature and species concentration assumed in the radial direction. In this work it is shown that the soot radial profiles of rich premixed ethylene-air flames produced by a McKenna burner with a stainless steel porous plug may be far from being ''flat.'' Soot is mainly distributed in an annular region and nonsoot fluorescing species are present in the core of the flames. This surprising result was verified under several working conditions. Furthermore, flames cannot be considered axial-symmetric but present a skewed soot distribution. Another McKenna burner with a bronze porous disk was used to produce flames of the same equivalence ratio and flows. These flames show a completely different soot radial profile, closer to the claimed flat distribution. These results cast doubts about the conclusions drawn in several studies on soot formation performed with a stainless steel McKenna burner. (author)

  4. Visualization of the heat release zone of highly turbulent premixed jet flames

    NASA Astrophysics Data System (ADS)

    Lv, Liang; Tan, Jianguo; Zhu, Jiajian

    2017-10-01

    Visualization of the heat release zone (HRZ) of highly turbulent flames is significantly important to understand the interaction between turbulence and chemical reactions, which is the foundation to design and optimize engines. Simultaneous measurements of OH and CH2O using planar laser-induced fluorescence (PLIF) were performed to characterize the HRZ. A well-designed piloted premixed jet burner was employed to generate four turbulent premixed CH4/air jet flames, with different jet Reynolds numbers (Rejet) ranging from 4900 to 39200. The HRZ was visualized by both the gradient of OH and the pixel-by-pixel product of OH and CH2O. It is shown that turbulence has an increasing effect on the spatial structure of the flame front with an increasing height above the jet exit for the premixed jet flames, which results in the broadening of the HRZ and the increase of the wrinkling. The HRZ remains thin as the Rejet increases, whereas the preheat zone is significantly broadened and thickened. This indicates that the smallest turbulent eddies can only be able to enter the flame front rather than the HRZ in the present flame conditions. The flame quenching is observed with Rejet = 39200, which may be due to the strong entrainment of the cold air from outside of the burned gas region.

  5. Bluff-body stabilized flame dynamics of lean premixed syngas combustion

    NASA Astrophysics Data System (ADS)

    Im, Hong G.; Kim, Yu Jeong; Lee, Bok Jik; Kaust Team

    2015-11-01

    Recently, syngas combustion has been actively investigated for the potential application to integrated gasification combined cycle (IGCC) systems. While lean premixed combustion is attractive for both reduced emission and enhanced efficiency, flame instability becomes often an issue. Bluff-bodies have been adopted as effective flame holders for practical application of premixed flames. In the present study, high-fidelity direct numerical simulations are conducted to investigate the dynamics of lean premixed syngas flames stabilized on a bluff-body, in particular at the near blow-off regime of the flame. A two-dimensional domain of 4 mm height and 20 mm length with a flame holder of a 1 mm-by-1 mm square geometry is used. For a syngas mixture with the equivalence ratio of 0.5 and the CO:H2 ratio of 1, several distinct flame modes are identified as the inflow velocity approaches to the blowoff limit. The sequences of extinction pathway and combustion characteristics are discussed.

  6. The role of reactant unmixedness, strain rate, and length scale on premixed combustor performance

    SciTech Connect

    Samuelsen, S.; LaRue, J.; Vilayanur, S.

    1995-10-01

    Lean premixed combustion provides a means to reduce pollutant formation and increase combustion efficiency. However, fuel-air mixing is rarely uniform in space and time. This nonuniformity in concentration will lead to relative increases in pollutant formation and decreases in combustion efficiency. The nonuniformity of the concentration at the exit of the premixer has been defined by Lyons (1981) as the {open_quotes}unmixedness.{close_quotes} Although turbulence properties such as length scales and strain rate are known to effect unmixedness, the exact relationship is unknown. Evaluating this relationship and the effect of unmixedness in premixed combustion on pollutant formation and combustion efficiency are an important part of the overall goal of US Department of Energy`s Advanced Turbine Systems (ATS) program and are among the goals of the program described herein. The information obtained from ATS is intended to help to develop and commercialize gas turbines which have (1) a wide range of operation/stability, (2) a minimal amount of pollutant formation, and (3) high combustion efficiency. Specifically, with regard to pollutants, the goals are to reduce the NO{sub x} emissions by at least 10%, obtain less than 20 PPM of both CO and UHC, and increase the combustion efficiency by 5%.

  7. Soot Formation in Laminar Premixed Methane/Oxygen Flames at Atmospheric Pressure. Appendix H

    NASA Technical Reports Server (NTRS)

    Xu, F.; Lin, K.-C.; Faeth, G. M.; Urban, D. L. (Technical Monitor); Yuan, Z.-G. (Technical Monitor)

    2001-01-01

    Flame structure and soot formation were studied within soot-containing laminar premixed methanefoxygen flames at atmospheric pressure. The following measurements were made: soot volume fractions by laser extinction, soot temperatures by multiline emission, gas temperatures (where soot was absent) by corrected fine-wire thermocouples, soot structure by thermophoretic sampling and transmission electron microscope (TEM), major gas species concentrations by sampling and gas chromatography, and gas velocities by laser velocimetry. Present measurements of gas species concentrations were in reasonably good agreement with earlier measurements due to Ramer et al. as well as predictions based on the detailed mechanisms of Frenklach and co-workers and Leung and Lindstedt; the predictions also suggest that H atom concentrations are in local thermodynamic equilibrium throughout the soot formation region. Using this information, it was found that measured soot surface growth rates could be correlated successfully by predictions based on the hydrogenabstraction/carbon-addition (HACA) mechanisms of both Frenklach and co-workers and Colket and Hall, extending an earlier assessment of these mechanisms for premixed ethylene/air flames to conditions having larger H/C ratios and acetylene concentrations. Measured primary soot particle nucleation rates were somewhat lower than the earlier observations for laminar premixed ethylene/air flames and were significantly lower than corresponding rates in laminar diffusion flames, for reasons that still must be explained.

  8. Soot Formation in Laminar Premixed Methane/Oxygen Flames at Atmospheric Pressure

    NASA Technical Reports Server (NTRS)

    Xu, F.; Lin, K.-C.; Faeth, G. M.

    1998-01-01

    Flame structure and soot formation were studied within soot-containing laminar premixed mc1hane/oxygen flames at atmospheric pressure. The following measurements were made: soot volume fractions by laser extinction, soot temperatures by multiline emission, gas temperatures (where soot was absent) by corrected fine-wire thermocouples, soot structure by thermophoretic sampling and transmission electron microscope (TEM), major gas species concentrations by sampling and gas chromatography, and gas velocities by laser velocimetry. Present measurements of gas species concentrations were in reasonably good agreement with earlier measurements due to Ramer et al. as well as predictions based on the detailed mechanisms of Frenklach and co-workers and Leung and Lindstedt: the predictions also suggest that H atom concentrations are in local thermodynamic equilibrium throughout the soot formation region. Using this information, it was found that measured soot surface growth rates could be correlated successfully by predictions based on the hydrogen-abstraction/carbon-addition (HACA) mechanisms of both Frenklach and co-workers and Colket and Hall, extending an earlier assessment of these mechanisms for premixed ethylene/air flames to conditions having larger H/C ratios and acetylene concentrations. Measured primary soot particle nucleation rates were somewhat lower than the earlier observations for laminar premixed ethylene/air flames and were significantly lower than corresponding rates in laminar diffusion flames. for reasons that still must be explained.

  9. Conditional budgets of second-order statistics in nonpremixed and premixed turbulent combustion

    NASA Astrophysics Data System (ADS)

    Macart, Jonathan F.; Grenga, Temistocle; Mueller, Michael E.

    2016-11-01

    Combustion heat release modifies or introduces a number of new terms to the balance equations for second-order turbulence statistics (turbulent kinetic energy, scalar variance, etc.) compared to incompressible flow. A major modification is a significant increase in viscosity and dissipation in the high-temperature combustion products, but new terms also appear due to density variation and gas expansion (dilatation). Previous scaling analyses have hypothesized that dilatation effects are important in turbulent premixed combustion but are unimportant in turbulent nonpremixed combustion. To explore this hypothesis, a series of DNS calculations have been performed in the low Mach number limit for spatially evolving turbulent planar jet flames of hydrogen and air in both premixed and nonpremixed configurations. Unlike other studies exploring the effects of heat release on turbulence, the turbulence is not forced, and detailed chemical kinetics are used to describe hydrogen-air combustion. Budgets for second-order statistics are computed conditioned on progress variable in the premixed flame and on mixture fraction in the nonpremixed flame in order to locate regions with respect to the flame structure where dilatation effects are strongest.

  10. Premixed calcium silicate cement for endodontic applications: injectability, setting time and radiopacity.

    PubMed

    Persson, Cecilia; Engqvist, Håkan

    2011-01-01

    Calcium silicate-based materials (also called MTA) are increasingly being used in endodontic applications. However, the handling properties of MTA are not optimal when it comes to injectability and cohesion. Premixing the cements using glycerol avoids these issues. However, there is a lack of data on the effect of common cement variables on important properties of premixed cements for endodontic applications. In this study, the effects of liquid-to-powder ratio, amount of radiopacifier and amount of calcium sulfate (added to control the setting time) were screened using a statistical model. In the second part of the study, the liquid-to-powder ratio was optimized for cements containing three different amounts of radiopacifier. Finally, the effect of using glycerol rather than water was evaluated in terms of radiopacity. The setting time was found to increase with the amount of radiopacifier when the liquid-to-powder ratio was fixed. This was likely due to the higher density of the radiopacifier in comparison to the calcium silicate, which gave a higher liquid-to-powder ratio in terms of volume. Using glycerol rather than water to mix the cements led to a decrease in radiopacity of the cement. In conclusion, we were able to produce premixed calcium silicate cements with acceptable properties for use in endodontic applications.

  11. Cost Analysis of Premixed Multichamber Bags Versus Compounded Parenteral Nutrition: Breakeven Point

    PubMed Central

    Bozat, Erkut

    2014-01-01

    Abstract Background: Industrially premixed multichamber bags or hospital-manufactured compounded products can be used for parenteral nutrition. The aim of this study was to compare the cost of these 2 approaches. Materials and Methods: Costs of compounded parenteral nutrition bags in an university hospital were calculated. A total of 600 bags that were administered during 34 days between December 10, 2009 and February 17, 2010 were included in the analysis. For quality control, specific gravity evaluation of the filled bags was performed. Results: It was calculated that the variable cost of a hospital compounded bag was $26.15. If we take the annual fixed costs into consideration, the production cost reaches $36.09 for each unit. It was estimated that the cost for the corresponding multichamber bag was $37.79. Taking the fixed and the variable costs into account, the breakeven point of the hospital compounded and the premixed multichamber bags was seen at 5,404 units per year. In specific gravity evaluation, it was observed that the mean and interval values were inside the upper and lower control margins. Conclusion: In this analysis, usage of hospital-compounded parenteral nutrition bags showed a cost advantage in hospitals that treat more than 15 patients per day. In small volume hospitals, premixed multichamber bags may be more beneficial. PMID:24623870

  12. An ergonomic analysis of premixing and compounding processes in an animal health plant.

    PubMed

    Lu, C; Goggins, W B

    1999-01-01

    This study is based on an ergonomic job analysis designed to develop a hazard prevention program for the premixing and compounding processes in animal health products plants. Animal health products plants are "pharmaceutical facilities" for livestock or domestic animals. A hazardous aerosol (highly concentrated antibiotics, anthelmintics, mineral oil, and animal hormones) is generated in the premixing or compounding processes. The animal health premixing jobs are heavy-duty jobs and have high potential for chemical exposure, heat stress, and ergonomic hazards. Ergonomic job analysis was used to recognize, identify, and evaluate actuarial and potential risks of injures or irritations. Chemical hazards and eight ergonomic factors were discussed: (1) forceful exertions, (2) awkward postures, (3) localized contract stresses, (4) vibration, (5) noise, (6) temperature extremes, (7) repetitive activities, and (8) prolonged activities. The results show that (1) current practices do not violate occupational safety and health regulations or recommended guidelines, but that hazards should be identified to protect worker health and safety; (2) for chemical hazards prevention, operators wear whole-body protection equipment, which also causes heat stress and increases the noise level in the work zone; and (3) the loading weight of the bags used needs to be reduced.

  13. Flow field studies of a new series of turbulent premixed stratified flames

    SciTech Connect

    Seffrin, F.; Fuest, F.; Dreizler, A.; Geyer, D.

    2010-02-15

    This paper presents a new burner design for lean premixed stratified combustion for experiments to validate models for numerical simulations. The burner demonstrates combustion phenomena relevant to technological applications, where flames are often turbulent, lean premixed, and stratified. The generic burner was designed for high Reynolds number flows and can stabilize a variety of different lean premixed flames. The burner's design and its versatile operational conditions are introduced. Shear, stratification, and fuel type are parametrically varied to provide a sound database of related flow configurations. Reacting and corresponding non-reacting configurations are examined. Experimental setups and the results of laser Doppler velocimetry (LDV) and particle image velocimetry (PIV) are presented and discussed. LDV measurements provide radial profiles of mean axial velocity, mean radial velocity, and turbulent kinetic energy as well as integral time scales. High-speed PIV is introduced as a novel technique to determine integral time and length scales and provide 2D 2-component velocity fields and related quantities, such as vorticity. (author)

  14. Direct Numerical Simulation of a Cavity-Stabilized Ethylene/Air Premixed Flame

    NASA Astrophysics Data System (ADS)

    Chen, Jacqueline; Konduri, Aditya; Kolla, Hemanth; Rauch, Andreas; Chelliah, Harsha

    2016-11-01

    Cavity flame holders have been shown to be important for flame stabilization in scramjet combustors. In the present study the stabilization of a lean premixed ethylene/air flame in a rectangular cavity at thermo-chemical conditions relevant to scramjet combustors is simulated using a compressible reacting multi-block direct numerical simulation solver, S3D, incorporating a 22 species ethylene-air reduced chemical model. The fuel is premixed with air to an equivalence ratio of 0.4 and enters the computational domain at Mach numbers between 0.3 and 0.6. An auxiliary inert channel flow simulation is used to provide the turbulent velocity profile at the inlet for the reacting flow simulation. The detailed interaction between intense turbulence, nonequilibrium concentrations of radical species formed in the cavity and mixing with the premixed main stream under density variations due to heat release rate and compressibility effects is quantified. The mechanism for flame stabilization is quantified in terms of relevant non-dimensional parameters, and detailed analysis of the flame and turbulence structure will be presented. We acknowledge the sponsorship of the AFOSR-NSF Joint Effort on Turbulent Combustion Model Assumptions and the DOE Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences.

  15. DNS of turbulent premixed slot flames with mixture inhomogeneity: a study of NOx formation

    NASA Astrophysics Data System (ADS)

    Luca, Stefano; Attili, Antonio; Bisetti, Fabrizio

    2016-11-01

    A set of Direct Numerical Simulations of three-dimensional methane/air lean flames in a spatially developing turbulent slot burner are performed. The flames are in the thin-reaction zone regimes and the jet Reynolds number is 5600. This configuration is of interest since it displays turbulent production by mean shear as in real devices. The gas phase hydrodynamics are modeled with the reactive, unsteady Navier-Stokes equations in the low Mach number limit. Combustion is treated with finite-rate chemistry. The jet is characterized by a non-uniform equivalence ratio at the inlet and varying levels of incomplete premixing for the methane/air mixture are considered. The global equivalence ratio is 0.7 and temperature is 800 K. All simulations are performed at 4 atm. The instantaneous profiles of the mass fractions of methane and air at the inlet are sampled from a set of turbulent channel simulations that provide realistic, fully turbulent fields. The data are analyzed to study the influence of partial premixing on the flame structure. Particular focus is devoted to the assessment of heat release rate fluctuations and NOx formation. In particular, the effects of partial premixing on the production rates for the various pathways to NOx formation are investigated.

  16. Gravitational Influences on Flame Propagation Through Non-Uniform, Premixed Gas Systems

    NASA Technical Reports Server (NTRS)

    Miller, Fletcher J.; Easton, John; Marchese, Anthony; Hovermann, Fred

    2003-01-01

    Flame propagation through non-uniformly premixed (or layered) gases has importance both in useful combustion systems and in unintentional fires. As summarized recently and in previous Microgravity Workshop papers, non-uniform premixed gas combustion receives scant attention compared to the more usual limiting cases of diffusion or uniformly premixed flames, especially regarding the role gravity plays. This paper summarizes our recent findings on gravitational effects on layered combustion along a floor, in which the fuel concentration gradient exists normal to the direction of flame spread. In an effort to understand the mechanism by which the flames spread faster in microgravity (and much faster, in laboratory coordinates, than the laminar burning velocity for uniform mixtures), we have begun making pressure measurements across the spreading flame front that are described here. Earlier researchers, testing in 1g, claimed that hydrostatic pressure differences could account for the rapid spread rates. Additionally, we present the development of a new apparatus to study flame spread in free (i.e., far from walls), non-homogeneous fuel layers formed in a flow tunnel behind an airfoil that has been tested in normal gravity.

  17. Gravitational Influences on Flame Propagation through Non-Uniform, Premixed Gas Systems

    NASA Technical Reports Server (NTRS)

    Miller, Fletcher J.; Easton, John; Ross, Howard D.; Marchese, Anthony; Perry, David; Kulis, Michael

    2001-01-01

    Flame propagation through non-uniformly premixed (or layered) gases has importance both in useful combustion systems and in unintentional fires. As summarized previously, non-uniform premixed gas combustion receives scant attention compared to the more usual limiting cases of diffusion or uniformly premixed flames, especially regarding the role gravity plays. This paper summarizes our progress on furthering the knowledge of layered combustion, in which a fuel concentration gradient exists normal to the direction of flame spread. We present experimental and numerical results for flame spread through propanol-air layers formed near the flash point temperature (25 C) or near the stoichiometric temperature (33 C). Both the model and experimental results show that the removal of gravity results in a faster spreading flame, by as much as 80% depending on conditions. This is exactly the opposite effect as that predicted by an earlier model reported. We also found that having a gallery lid results in faster flame spread, an effect more pronounced at normal gravity, demonstrating the importance of enclosure geometry. Also reported here is the beginning of our spectroscopic measurements of fuel vapor.

  18. On the Structure and Stabilization Mechanisms of Planar and Cylindrical Premixed Flames

    NASA Technical Reports Server (NTRS)

    Eng, James A.; Zhu, Delin; Law, Chung K.

    1993-01-01

    The configurational simplicity of the stationary one-dimensional flames renders them intrinsically attractive for fundamental flame structure studies. The possibility and fidelity of studies of such flames on earth, however, have been severely restricted by the unidirectional nature of the gravity vector. To demonstrate these complications, let us first consider the premixed flame. Here a stationary, one-dimensional flame can be established by using the flat-flame burner. We next consider nonpremixed flames. First it may be noted that in an unbounded gravity-free environment, the only stationary one-dimensional flame is the spherical flame. Indeed, this is a major motivation for the study of microgravity droplet combustion, in which the gas-phase processes can be approximated to be quasi-steady because of the significant disparity between the gas and liquid densities for subcritical combustion. In view of the above considerations, an experimental and theoretical program on cylindrical and spherical premixed and nonpremixed flames in microgravity has been initiated. For premixed flames, we are interested in: (1) assessing the heat loss versus flow divergence as the dominant stabilization mechanism; (2) determining the laminar flame speed by using this configuration; and (3) understanding the development of flamefront instability and the effects of the flame curvature on the burning intensity.

  19. All about Insulin Resistance

    MedlinePlus

    Toolkit No. 2 All About Insulin Resistance Insulin resistance is a condition that raises your risk for type 2 diabetes and heart disease. ... Diabetes Association, Inc. 1/15 Toolkit No. 2: All About Insulin Resistance continued J Order the smallest ...

  20. Economic evaluation of the treatment of type 2 diabetes with insulin glargine based on the LAPTOP trial.

    PubMed

    Janka, Hans Uwe; Högy, Barbara

    2008-05-01

    In the LAPTOP trial, combination therapy with once-daily insulin glargine + oral antidiabetic agents glimepiride and metformin (BOT) was compared to twice-daily premixed insulin (CT). BOT was safer and more effective than CT. Cost analysis of both regimens were compared over a 1-year period. Analyses were performed from the perspective of the German statutory health insurance. Costs per patient per year were on average 236euro lower for BOT than for CT therapy. Economic advantage for BOT was robust to variation of expenses within a range of at least +/-20%. Insulin utilisation and prices were the major cost drivers, followed by costs associated with monitoring of blood glucose levels. Cost analysis of the LAPTOP trial suggest that BOT is more cost effective alternative to CT.

  1. A theoretical and experimental study of preferential-diffusion/stretch interactions of laminar premixed flames

    NASA Astrophysics Data System (ADS)

    Kwon, Oh Chae

    Recent work shows that preferential-diffusion/stretch interactions of laminar premixed flames are sufficiently robust to affect the stability of practical strongly-turbulent flames. In addition, past measurements of laminar burning velocities should be re-assessed because there generally was no attempt to control flame stretch. Finally, the sensitivity of laminar premixed flames to stretch (represented by the Markstein number) should be studied to better understand and model the properties of laminar premixed flames. Motivated by these considerations, an experimental and computational study of preferential-diffusion/stretch interactions for laminar premixed flames, for both alkane/alcohol-fuel-vapor-fueled flames (as practical fuels) and hydrogen-fueled flames (considering diluent-variation effects) was carried out during the present investigation. Considering outwardly-propagating spherical laminar premixed flames, laminar burning velocities of fuel-vapor/oxygen/nitrogen flames and hydrogen/oxygen/diluent (nitrogen, argon or helium) flames were measured for various values of stretch, fuel-equivalence ratios (0.6--4.5) and pressures (0.3--3 atm). The measurements were reduced to find fundamental unstretched laminar burning velocities and Markstein numbers. The measurements were also used to evaluate corresponding numerical simulations of the experimentally-observed flames, based on contemporary detailed H2/O2 reaction mechanisms. Both measured and predicted ratios of unstretched to stretched laminar burning velocities varied linearly with flame stretch (represented by the Karlovitz number), yielding a constant Markstein number for a particular reactant mixture. The present flames were very sensitive to flame stretch (i.e., they had large Markstein numbers with significant ratios of unstretched to stretched laminar burning velocities) for levels of flame stretch well below quenching conditions. Increasing flame temperatures tended to reduce flame sensitivity to

  2. Incorporating a Generic Model of Subcutaneous Insulin Absorption into the AIDA v4 Diabetes Simulator: 1. A Prospective Collaborative Development Plan

    PubMed Central

    Lehmann, Eldon D.; Tarín, Cristina; Bondia, Jorge; Teufel, Edgar; Deutsch, Tibor

    2007-01-01

    Introduction AIDA v4 is an interactive educational diabetes simulator that has been made available, for over a decade, without charge via the Internet. The software is currently freely accessible at http://www.2aida.org. This report sets out a collaborative development plan to enhance the program with a new model of subcutaneous insulin absorption,